Precursor T-cell lymphoblastic lymphoma

— Previously reported Phase 1/2 data on WU-CART-007 demonstrated clinically manageable safety and evidence of anti-leukemic activity with an overall response rate of 91% and composite complete remission rate of 73% in heavily pretreated patients with R/R T-ALL/LBL — The global pivotal Phase 2 T-RRex Study will evaluate WU-CART-007 in pediatric and adult patients ST. LOUIS, MO, USA I March 20, 2025 I Wugen, Inc., a clinical-stage U.S. biotechnology company developing allogeneic, off-the-shelf cell therapies for the treatment of hematological and solid tumor malignancies, today announced the dosing of the first patients in its pivotal Phase 2 study evaluating WU-CART-007, a potential first-in-class, investigational, anti-CD7 CAR-T cell therapy 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 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. “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. 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.” Wugen previously announced positive results from a Phase 1/2 cohort expansion study showing clinically manageable safety and evidence of anti-leukemic activity (overall response rate of 91%; composite complete remission rate of 73%) in heavily pretreated patients with R/R T-ALL/LBL. Results were presented at both the American Society of Hematology Annual Meeting (ASH) in December of 2024 and the European Hematology Association (EHA) 2024 Hybrid Congress in June of 2024. “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,” said 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. The enthusiasm around the program and the need for new treatments have been reflected in the study recruitment thus far, as it is enrolling faster than anticipated.” Pivotal Study Design: The pivotal study entitled, “A Phase 2 Study of WU-CART-007, an Anti-CD7 Allogeneic CAR-T Cell Therapy in Patients with Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma”, (T-RRex) is a single arm trial evaluating the efficacy and safety of WU-CART-007 in patients with R/R T-ALL/LBL and T-ALL/LBL. The study will involve two groups: a R/R cohort and subsequently an exploratory minimal residual disease (MRD)-positive cohort. About WU-CART-007 WU-CART-007 is an allogeneic, off-the-shelf, fratricide-resistant CD7-targeted CAR-T cell therapy engineered to overcome the technological challenges of harnessing CAR-T cells to treat CD7+ hematological malignancies. Wugen is deploying CRISPR/Cas9 gene editing technology to delete CD7 and the T cell receptor alpha constant (TRAC), preventing CAR-T cell fratricide and mitigating the risk of graft-versus-host-disease (GvHD). WU-CART-007 is manufactured using healthy donor-derived T cells to eliminate the risk of malignant cell contamination historically observed in the autologous CAR-T setting. WU-CART-007 is currently being evaluated in a global Phase 1/2 clinical trial for the treatment of relapsed or refractory (R/R) T cell acute lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (LBL). More information on the Phase 1/2 trial is available on clinicaltrials.gov, identifier NCT# 04984356 and on the Phase 2 pivotal trial on clinicaltrials.gov, identifier NCT06514794. WU-CART-007 has received Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration and Priority Medicines (PRIME) Scheme designation in the European Union for the treatment of relapsed/refractory (R/R) T cell acute lymphoblastic leukemia (T-ALL) and T cell lymphoblastic lymphoma (T-LBL). RMAT and PRIME designations provide increased agency support to expedite the development and review of promising therapies for patients in need. About Wugen Wugen, Inc. is a clinical-stage U.S. biotechnology company developing the next generation of off-the-shelf CAR-T and memory natural killer (NK) cell therapies for cancer. For more information, please visit www.wugen.com and follow Wugen’s LinkedIn page. SOURCE: Wugen

Despite investor doubt in allogeneic cell therapy, 2023 will be an “important” year for both autologous and allogeneic immune-cell-based therapies in multiple myeloma and non-Hodgkin’s lymphoma, SVB analysts predict. With drug candidates like mosunetuzumab, glofitamab and epcoritamab making their way through clinical trials, SVB Securities analysts are predicting the commercialization of bispecific CD3 T-cell engagers will begin to be a part of treatment paradigms as these drugs get approved. “We expect maturation of these markets will be multi-year journeys, impacted by (lack of) necessary infrastructure and training in the community setting to deliver TCEs, slow release of manufacturing constraints for auto CAR-T, as well as ongoing data disclosures in earlier lines, from combinations, and with class sequencing,” SVB analysts wrote in a lengthy report released Tuesday. Analysts also had a critique for the American Society for Hematology (ASH) meeting where there was undue investor pessimism toward allogeneic therapies: “For us, this is overdone, with much of the allogeneic criticism premature, given allogeneic cell therapies are in the nascent stages of clinical development.” Allogeneic T-cell therapy took a big step forward in Europe last month with the approval of the first one on the continent. The European Commission signed off on Ebvallo , made by Atara Biotherapeutics, for patients with post-transplant lymphoproliferative disease who are positive for Epstein-Barr virus. Other clinical trials with Ebvallo are ongoing. Also last month, Beam Therapeutics got the go-ahead from the FDA to continue with human testing for a base-edited, off-the-shelf CAR-T therapy in a certain type of leukemia. Beam can now investigate its candidate BEAM-201 as a potential treatment for patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LL). Beam is one of several biotechs working on an allogeneic CAR-T therapy, which requires donor cells rather than a patient’s own cells. The SVB analysts also took a look at what’s coming for non-Hodgkin’s lymphoma treatment, including mosunetuzumab, which just earned an FDA accelerated approval. Analysts are also keeping tabs on other FDA actions yet to come: the first potential bispecific engager approvals for 3L+ large B-cell lymphoma like epcoritamab, which was granted priority review, and an anticipated July 2023 PDUFA date for Roche’s glofitamab. “We also anticipate numerous Ph 1/2 updates from the bispecifics and the autologous and allogeneic cell therapies throughout the year,” the analysis reads. “Of these, initial Ph 1 data from DTIL’s (Not Rated) second-generation allogeneic CD19-CAR-T candidate, PBCAR19B, in 1Q23 could prove a particularly important catalyst for all allo cell therapy developers, given that the program incorporates multiple immune evasion, or “stealth”, modalities.”

Al Drago/CQ Roll Call The FDA has lifted its clinical hold on Beam Therapeutics’ BEAM-201 and cleared the way for an Investigational New Drug Application, the company announced Friday. Al Drago/CQ Roll Call/Getty Images The FDA has lifted its clinical hold on Beam Therapeutics ’ BEAM-201 and cleared the way for an Investigational New Drug Application, the company announced Friday. BEAM-201 is an anti-CD7, multiplex-edited, allogeneic chimeric antigen receptor T cell (CAR-T) development candidate. The company is gearing up to trial the experimental cell therapy as a potential treatment for relapsed/refractory T cell acute lymphoblastic leukemia (T-ALL)/T cell lymphoblastic lymphoma (T-LL). The Cambridge biotech announced in August that the FDA placed a clinical hold on the therapy. Beam revealed the reasons for the FDA’s hold in a subsequent SEC report, filed late August. As stated in its formal letter, the regulatory body requested additional control data from the genomic rearrangement studies, as well as further analyses of off-target editing experiments. The agency also needed more control data for a specific cytokine-independent growth assay and asked for an updated investigator brochure with information on any new non-clinical studies. In its Q3 financial results released in early November, Beam noted it had already responded to the FDA’s requests. Using proprietary technologies, BEAM’s base editors work by chemically transforming one nucleotide base into another. BEAM-201 is designed to side-step current logistical and technical limitations of CAR-T treatments by simultaneously affecting many target genes, potentially allowing for universal compatibility, as well as resistance to immunosuppression and host rejection. In a statement, BEAM CEO John Evans said that the FDA’s lift of its clinical hold marks “the first IND clearance for a multiplex-base edited investigational drug,” and could lead to an innovative and effective treatment for patients with few therapeutic options for their disease. Beam’s stock rose some 6% premarket in reaction to the news. The Next Step in Gene Editing Most gene therapies break both strands of the DNA to introduce genetic changes. This approach, while effective, has long been known to yield substantial off-target effects, which are induced genetic mutations at loci other than the target site. In turn, this could lead to safety concerns and toxicities. In contrast, base editors make use of chemical reactions to change one base pair into another. The first-ever editor, for instance, was developed in 2016 and made used a specific deaminase enzyme to change a cytosine-guanine into a thymine-adenine pair. This approach is not only safe, yielding fewer off-target effects, but also turns out to be more efficient than typical gene editing, especially when it comes to point mutations. There are other early adopters of base editing in biopharma, including Verve Therapeutics , which has licensed its base editing technology from Beam and is testing it against heterozygous familial hypercholesterolemia. The FDA also put Verve’s lead candidate on hold earlier this month. Another is Metagenomi , which develops “next-generation therapies” using base editing technologies, alongside more typical CRISPR-based gene editing approaches.