letetresgene autoleucel (GSK3377794) / Adaptimmune, US WorldMeds - LARVOL DELTA

US WorldMeds Completes Acquisition of Adaptimmune's Cell-Therapy Portfolio; Ensures Continued Patient Access to Tecelra and Advances Development of lete-cel (PRNewswire) - "US WorldMeds (USWM) reported the successful closing of the previously announced acquisition of Adaptimmune Therapeutics plc's (Adaptimmune) cell–therapy assets-including TECELRA (afamitresgene autoleucel), lete–cel, afami–cel, and uza–cel. The acquisition was first announced on July 28, 2025 and has now been finalized. Under the terms of the Asset Purchase Agreement, USWM paid $55 million in cash at closing and will fund up to an additional $30 million in performance-based milestone payments tied to commercial and regulatory outcomes....Key Highlights: (i) Patient care continuity: TECELRA will remain available to patients without interruption, now under USWM's stewardship; (ii) Future development: USWM plans to bring lete–cel to the U.S. market, with potential regulatory approval anticipated in 2026, and will continue development of uza–cel in collaboration with Galapagos."

Commercial • FDA approval • Liposarcoma • Spindle Cell Sarcoma • Synovial Sarcoma

Adaptimmune Announces Entry into Definitive Agreement for Sale of TECELRA, lete-cel, afami-cel and uza-cel Cell Therapies to US WorldMeds (Adaptimmune Press Release) - "Adaptimmune Therapeutics plc...announced its entry into a definitive agreement for the sale of TECELRA, lete-cel, afami-cel, and uza-cel cell therapies to US WorldMeds. Consummation of the sale is expected to occur before the end of the week....Adaptimmune will retain rights to its preclinical assets including PRAME, CD70, and its allogeneic program; Adaptimmune will restructure to support the transition of these therapies to US WorldMeds and to maximize value from its remaining assets."

Commercial • Spindle Cell Sarcoma • Synovial Sarcoma

Adaptimmune Reports Q1 Financial Results and Provides Business Update (Adaptimmune Press Release) - "TECELRA launch 2025 YTD metrics: 28 ATCs available; 21 patients aphresed; and 14 doses invoiced; $4.0 million Tecelra net sales in Q1 2025....Initiate rolling BLA for lete-cel to treat synovial sarcoma and MRCLS in Q4 2025."

FDA filing • Launch • Sales • Liposarcoma • Sarcoma • Synovial Sarcoma

Safety and Tolerability of Lete-cel in NSCLC-Letter. (PubMed, Clin Cancer Res) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Safety and Tolerability of Lete-cel in NSCLC-Reply. (PubMed, Clin Cancer Res) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Review of Adoptive Cellular Therapies for the Treatment of Sarcoma. (PubMed, Cancers (Basel)) - "Engineered TCRs, particularly those targeting MAGE-A4 and NY-ESO-1, have shown promising clinical results in synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS), leading to the recent FDA approval of afamitresgene autoleucel (afami-cel) and letetresgene autoleucel (lete-cel)...Future research will focus on optimizing lymphodepleting regimens, mitigating toxicity, enhancing in vivo persistence, and combining ACT with other therapeutic agents. As clinical trials expand, ACT holds the potential to revolutionize sarcoma treatment by offering durable, targeted therapies for previously refractory disease."

Journal • Review • Hematological Malignancies • Liposarcoma • Melanoma • Multiple Myeloma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CD276 • CTAG1B • HER-2 • MAGEA4

Letetresgene Autoleucel: A Milestone in Treatment of Myxoid/Round Cell Liposarcoma. (PubMed, J Clin Oncol) - No abstract available

Journal • Liposarcoma • Oncology • Sarcoma • Solid Tumor

Adaptimmune Provides Q4 and Full Year 2024 Business Update (Adaptimmune Press Release) - "Lete-cel on track to initiate rolling BLA submission late 2025; approval anticipated 2026...Implemented additional cost reduction for the PRAME and CD70 programs. The Company anticipates this will generate an additional $75m to $100m in aggregate cost savings over the next 4 years."

FDA approval • FDA filing • Pricing • Oncology • Soft Tissue Sarcoma • Synovial Sarcoma

AGC, AdaptiMune and Lentiviral Vector Commercial Production Collaboration [Google translation] (HIT News) - "AGC Biologics announced a collaboration with Adaptimune to support commercial manufacturing of lentiviral vectors for the production of letetresgene autoleucel, a next-generation T cell receptor (TCR)-based cell therapy....Under the agreement, AGC Biologics will manufacture the lentiviral vectors required for lete-cel production and will support Adaptimmune’s Biologics License Application (BLA) through process characterization, stability studies, and vector supply."

Commercial • Liposarcoma • Synovial Sarcoma

Letetresgene Autoleucel in Advanced/Metastatic Myxoid/Round Cell Liposarcoma. (PubMed, J Clin Oncol) - P2 | "To our knowledge, this study is the first demonstrating the clinical promise of lete-cel in HLA-/NY-ESO-1-positive patients with advanced MRCLS."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Hematological Disorders • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • CTAG1B • HLA-A

Letetresgene Autoleucel in Advanced/Metastatic Myxoid/Round Cell Liposarcoma (J Clin Oncol) - P2 | N=23 | NCT02992743 | Sponsor: GlaxoSmithKline | "Of 23 enrolled patients, 10 in cohort 1 and 10 in cohort 2 received lete-cel. Investigator-assessed ORR was 20% (95% CI, 2.5 to 55.6) and 40% (95% CI, 12.2 to 73.8), median duration of response was 5.3 months (95% CI, 1.9 to 8.7) and 7.5 months (95% CI, 6.0 to not estimable [NE]), and median progression-free survival was 5.4 months (95% CI, 2.0 to 11.5) and 8.7 months (95% CI, 0.9 to NE) in cohorts 1 and 2, respectively. AEs included cytokine release syndrome and cytopenias, consistent with T-cell therapy/LDR."

P2 data • Liposarcoma

Adaptimmune Announces U.S. FDA Breakthrough Therapy Designation Granted to Letetresgene Autoleucel (lete-cel) for Treatment of Myxoid/Round Cell Liposarcoma (MRCLS) (Adaptimmune Press Release) - "Adaptimmune Therapeutics plc...announced that letetresgene autoleucel (lete-cel), has been granted breakthrough therapy designation by the U.S. FDA for the treatment of patients with unresectable or metastatic myxoid/round cell liposarcoma (MRCLS) who have received prior anthracycline-based chemotherapy, are positive for HLA-A*02:01, HLA-A*02:05, or HLA-A*02:06, and whose tumor expresses the NY-ESO-1 antigen....Breakthrough therapy designation for lete-cel in MRCLS was based on the results in this indication from the Phase II IGNYTE-ESO trial."

Breakthrough therapy • Liposarcoma

Safety and Tolerability of Letetresgene Autoleucel (Lete-cel; GSK3377794): Pilot Studies in Patients With Advanced Non-Small Cell Lung Cancer. (PubMed, Clin Cancer Res) - "Extensive HLA-A*02 and antigen expression testing was performed to identify potential participants. Lete-cel was generally well tolerated and had no unexpected AEs. Anti-tumor activity was observed in a limited number of patients."

IO biomarker • Journal • Metastases • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • CTAG1B • CTAG2 • HLA-A

Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants with NY-ESO-1 Positive Previously Treated Advanced (Metastatic or Unresectable) Synovial Sarcoma or Myxoid/Round Cell Liposarcoma (clinicaltrials.gov) - P2 | N=87 | Active, not recruiting | Sponsor: Adaptimmune

Metastases • New P2 trial • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

PLANNED ANALYSIS OF THE PIVOTAL IGNYTE-ESO TRIAL OF LETE-CEL IN PATIENTS WITH SYNOVIAL SARCOMA OR MYXOID/ROUND CELL LIPOSARCOMA. (CTOS 2024) - No abstract available

Clinical • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Adaptimmune virtual KOL event November 18th (Adaptimmune Press Release) - "Adaptimmune will host a virtual event to discuss and review the IGNYTE-ESO dataset and the impact of engineered cell therapies on the treatment landscape in sarcoma."

P2 data • Synovial Sarcoma

Adaptimmune's Lete-cel Achieves Primary Endpoint in Pivotal Trial (Adaptimmune Press Release) - P2 | N=103 | IGNYTE-ESO (NCT03967223) | Sponsor: Adaptimmune | "In the analysis, 27/64 (42%) people with synovial sarcoma or MRCLS had RECISTv1.1 responses by independent review, with six complete responses and 21 partial responses. The response rate was 14/34 (41%) for people with synovial sarcoma and 13/30 (43%) for people with MRCLS. The median duration of response (DoR) was 12.2 months (95% CI 6.8, 19.5). In synovial sarcoma, the median duration of response was 18.3 months (95% CI 3.3, -)....Data to be presented at Connective Tissue Oncology Society 2024 Annual Meeting; Company plans to initiate a rolling BLA submission for lete-cel for the treatment of advanced or metastatic synovial sarcoma and MRCLS by end of 2025."

FDA filing • P2 data • Synovial Sarcoma

Adaptimmune to Participate in Scientific and Medical Conferences this November and December (Adaptimmune Press Release) - "Adaptimmune Therapeutics plc...announced presence and presentations at key scientific and medical conferences in November and December. [1] Society for Immunotherapy of Cancer (SITC) 39th annual meeting, November 6-10, Houston, TX; [2] Connective Tissue Oncology Society (CTOS) 2024 annual meeting, November 13-16, San Diego, CA; [3] American Society of Hematology (ASH) 66th Annual Meeting, December 7-10, San Diego, CA."

Clinical data • Liposarcoma • Synovial Sarcoma

Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma (clinicaltrials.gov) - P2 | N=7 | Active, not recruiting | Sponsor: Adaptimmune | Trial completion date: Jul 2024 ➔ Jul 2025

Metastases • Trial completion date • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • HLA-A

Adaptimmune to Present Data from Planned Interim Analysis of Pivotal IGNYTE-ESO Trial with Lete-cel at ASCO; Data Continue to Support further Development of Sarcoma Franchise (Adaptimmune Press Release) - P2 | N=103 | IGNYTE-ESO (NCT03967223) | Sponsor: Adaptimmune | "'We look forward to sharing the full results of the IGNYTE-ESO trial in late 2024. We continue to work toward commercializing afami-cel later this year and lete-cel in 2026'....The overall response rate (ORR) of 40% was consistent across both SyS and MRCLS, and markedly greater than historical standard of care outcomes in these indications. The primary endpoint success criterion for efficacy was met by the interim analysis 40% ORR....The complete primary analyses from IGNYTE-ESO, including more mature duration of response, are currently in progress with a full dataset anticipated in late 2024....Given the success of the pivotal IGNYTE-ESO trial, Adaptimmune plans to initiate a rolling Biologics License Application (BLA) submission for lete-cel for the treatment of advanced or metastatic MRCLS and synovial sarcoma during 2025."

BLA • Launch • P2 data • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma

Lete-cel in patients with synovial sarcoma or myxoid/round cell liposarcoma: Planned interim analysis of the pivotal IGNYTE-ESO trial. (ASCO 2024) - P2 | "LD (fludarabine 120 mg/m 2 , cyclophosphamide 2700–3600 mg/m 2 , cumulative) was dose reduced for predefined risk factors. IGNYTE-ESO SS2 met the primary endpoint success criterion at this planned IA, with a 40% ORR consistent across SyS and MRCLS, and a known safety profile of hematologic toxicity and CRS. This supports the potential of lete-cel as a novel therapy for pts with advanced or metastatic SyS and MRCLS."

Clinical • Anemia • Hematological Disorders • Leukopenia • Liposarcoma • Neutropenia • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • Thrombocytopenia • CTAG1B

Adaptimmune Secures up to $125 Million Debt Financing with Hercules Capital (Adaptimmune Press Release) - "Adaptimmune Therapeutics plc...announced that it has entered into a $125 million five-year, term loan facility with Hercules Capital, Inc. (NYSE: HTGC) ('Hercules'). The transaction strengthens the Company's balance sheet as it executes on its sarcoma franchise with the commercial launch of afami-cel later this year and lete-cel planned for 2026. The Company will host a live webcast at 8:00 a.m. EDT (1:00 p.m. BST) today to report its Q1 financial and business updates."

Financing • Launch • Oncology

Adaptimmune Reports Q1 2024 Financial and Business Updates (Adaptimmune Press Release) - "Data from the planned interim analysis of the pivotal IGNYTE-ESO trial with lete-cel to be presented by Dr. Sandra P. D'Angelo, M.D., Sarcoma Medical Oncology, Memorial Sloan Kettering Cancer Center, in an oral presentation at ASCO...during the Developmental Therapeutics-Immunotherapy session in Hall D2 on June 3, 2024 at 11:30 a.m. CDT."

P2 data • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

IGNYTE-ESO: Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Solid Tumors (clinicaltrials.gov) - P2 | N=103 | Active, not recruiting | Sponsor: Adaptimmune | Trial primary completion date: Nov 2022 ➔ Aug 2024

Combination therapy • Trial primary completion date • Oncology • Solid Tumor • CTAG1B • HLA-A

Pilot Immunotherapy Study With Letetresgene Autoleucel (Lete-cel, GSK3377794)T-cells in New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1)/ LAGE-1a-positive Advanced Non-small Cell Lung Cancer (NSCLC) Either Alone or in Combination With Pembrolizumab (clinicaltrials.gov) - P1/2 | N=34 | Terminated | Sponsor: GlaxoSmithKline | Phase classification: P1b/2a ➔ P1/2

Combination therapy • Metastases • Phase classification • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • CTAG1B • CTAG2 • HLA-A • PD-L1