uzatresgene autoleucel (ADP-A2M4CD8) / Adaptimmune, Galapagos, US WorldMeds - LARVOL DELTA

Preclinical Proof of Concept for Decentralized Manufacturing of a MAGE-A4/CD8alpha-Expressing Autologous T-Cell Therapy for Solid Tumors (ASH 2024) - P1, P2 | "We investigated suitability of a decentralized, rapid, and fresh cell manufacturing platform to produce T cells expressing the MAGE-A4 TCR and CD8α co-receptor compared with the established central manufacturing process for uza-cel. Importantly, the GDM platform could significantly reduce total vein-to-vein time for eligible patients from several weeks to ~1 week. The GDM system will be used to supply MAGE-A4/CD8α–expressing T cells for a proof-of-concept clinical trial to assess their safety and efficacy in patients with advanced head and neck cancer."

IO biomarker • Preclinical • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • Urothelial Cancer • CD4 • IFNG • MAGEA4

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

ADP-A2M4CD8 As Monotherapy or in Combination with Either Nivolumab or Pembrolizumab in HLA-A2+ Subjects with MAGE-A4 Positive Tumors (SURPASS) (clinicaltrials.gov) - P1 | N=120 | Active, not recruiting | Sponsor: Adaptimmune | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Urothelial Cancer • HLA-A • MAGEA4

Galapagos Reports Full Year 2024 Results and Provides Fourth Quarter Business Update (GlobeNewswire) - "We are deprioritizing activities related to GLPG5201, our second CD19 CAR-T candidate, pending the advancement of GLPG5101 in those additional indications.....The Company plans to initiate clinical development of a novel CAR-T candidate in 2025 and expand its clinical pipeline of next-generation programs with the addition of two new clinical assets in 2026....Galapagos presented strong preclinical proof-of-concept data at ASH for uza-cel, a MAGE-A4 directed TCR T-cell therapy candidate in head and neck cancer, in partnership with Adaptimmune....Preparations are ongoing with the goal to start clinical development in 2026."

New trial • Pipeline update • Head and Neck Cancer • Hematological Malignancies

ADP-A2M4CD8 Monotherapy and in Combination with Nivolumab in HLA-A2+ Subjects with MAGE-A4 Positive Ovarian Cancer (SURPASS-3) (clinicaltrials.gov) - P2 | N=66 | Active, not recruiting | Sponsor: Adaptimmune | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Oncology • Ovarian Cancer • Solid Tumor • BRCA • HLA-A • MAGEA4 • PARP1

Adaptimmune Reports Q3 2024 Financial and Business Updates (Adaptimmune Press Release) - "The Company will cease enrolment in the SURPASS-3 Phase 2 clinical trial (NCT05601752), investigating uza-cel for the treatment of platinum-resistant ovarian cancer....Tecelra Launch:...9 Sarcoma centers of excellence across the U.S. are available as Authorized Treatment Centers (ATCs) for Tecelra and are accepting patients and referrals from healthcare providers to initiate the Tecelra treatment journey. The Company is confident the full ATC network of approximately 30 ATCs will be active by the end of 2025, covering an estimated 80% of patients treated in sarcoma centers of excellence. The first patient has been apheresed and first manufacture of Tecelra is ongoing."

Enrollment status • Launch US • Ovarian Cancer • Synovial Sarcoma

Galapagos to Present Results of Pioneering Innovation in Cancer Cell Therapy at ASH 2024 (GlobeNewswire) - "The data to be presented are summarized below:...The poster presentation for uza-cel, a MAGE-A4 directed TCR T-cell therapy candidate in head & neck (H&N) cancer, in partnership with Adaptimmune, will highlight preclinical proof-of-concept data demonstrating that Galapagos’ innovative decentralized cell therapy manufacturing platform can produce uza-cel with features that may result in improved efficacy and durability of response in the clinic compared with the existing manufacturing procedure."

Preclinical • Head and Neck Cancer

Galapagos Reports Third Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "We will present new data from the ATALANTA-1 and EUPLAGIA-1 studies along with pre-clinical data for uza-cel, our TCR-T cell therapy candidate produced on our decentralized manufacturing platform in collaboration with Adaptimmune, at the American Society of Hematology (ASH) Annual Meeting in December...We further advanced our early-stage proprietary pipeline and progressed a next-generation armed, bispecific CAR-T candidate in hemato-oncology and a potential best-in-class small molecule candidate in immunology into IND-enabling studies, targeting clinical development in 2025-2026; We are accelerating our early-stage pipeline of more than 15 programs in oncology and immunology with the objective of launching at least four IND/CTA-enabling studies in 2025 across different modalities and indications. From 2026 onward, our ambition is to fuel the clinical pipeline with at least two new clinical assets annually in various indications and across our cell therapy and small molecule..."

Clinical data • Pipeline update • Preclinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Adaptimmune Reports Q2 2024 Financial and Business Updates (Adaptimmune Press Release) - "Adaptimmune Therapeutics plc...reports financial results and business updates for the second quarter ended June 30, 2024...Sarcoma centers of excellence across the Unites States are being onboarded as Authorized Treatment Centers (ATCs) for Tecelra...Uza-cel is being investigated in the SURPASS-3 Phase 2 clinical trial (NCT05601752) for the treatment of platinum-resistant ovarian cancer...The SURPASS-3 trial is currently enrolling patients; Screening in the SURPASS Phase 1 trial has stopped and enrolment will cease shortly....IND-enabling activities continue for ADP-600 (PRAME) and ADP-520 (CD70) programs."

Commercial • Enrollment status • Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma

Advanced spatial biology techniques elucidate mechanisms of uza-cel's TCR-directed anti-tumor activity (EACR 2024) - P1 | "Additionally, HLA-DR enrichment at baseline and post-infusion highlights a potential marker of response to uza-cel. Our data provides further translational insight into the TME and anti-tumor activity observed in uza-cel patient biopsies."

IO biomarker • Late-breaking abstract • Metastases • Oncology • Solid Tumor • B2M • GZMB • HLA-DRA • HLA-DRB4 • MAGEA4 • PTPRC • TAP1

ADP-A2M4CD8 Monotherapy and in Combination With Nivolumab in HLA-A2+ Subjects With MAGE-A4 Positive Ovarian Cancer (SURPASS-3) (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: Adaptimmune | Trial completion date: Oct 2025 ➔ Aug 2026 | Trial primary completion date: Oct 2025 ➔ Aug 2026

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor • BRCA • HLA-A • MAGEA4 • PARP1

Galapagos and Adaptimmune sign clinical collaboration agreement with an option to exclusively license Adaptimmune’s TCR T-cell therapy candidate, uza-cel, in head & neck cancer and potential future solid tumor indications (GlobeNewswire) - "Galapagos NV...and Adaptimmune Therapeutics plc...announced today that they have entered into a clinical collaboration agreement with an option to exclusively license Adaptimmune’s next-generation TCR T-cell therapy (uza-cel) targeting MAGE-A4 for head & neck cancer and potential future solid tumor indications, using Galapagos’ decentralized cell manufacturing platform....Under the terms of the agreement, Adaptimmune will receive an upfront exclusivity payment of $70 million, plus $15 million in R&D funding at signing. A further $15 million in R&D funding will follow subject to the start of dosing in the proof-of-concept trial. Adaptimmune will be responsible for the clinical proof-of-concept trial in head & neck cancer and the supply of the vector for the manufacturing of uza-cel."

Licensing / partnership • Head and Neck Cancer

ADP-A2M4CD8 in HLA-A2+ Subjects With MAGE-A4 Positive Esophageal or Esophagogastric Junction Cancers (SURPASS-2) (clinicaltrials.gov) - P2 | N=3 | Terminated | Sponsor: Adaptimmune | N=45 ➔ 3 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2023 ➔ Apr 2023; Study was terminated due to difficulty recruiting subjects and lack of efficacy

Enrollment change • Metastases • Trial primary completion date • Trial termination • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • HLA-A • MAGEA4

GOG-3084: A phase II trial of ADP-A2M4CD8 TCR-T cell therapy, alone or in combination with nivolumab, among patients with recurrent ovarian cancers (SGO 2024) - P1, P2 | "Key eligibility criteria include: histologically confirmed high-grade serous or endometrioid recurrent/progressive platinum-resistant ovarian cancer; must have received bevacizumab; measurable disease per RECIST v1.1; MAGE-A4 expression at or above the designated threshold; positive for HLA-A*02:01P, 02:02P, 02:03P, or 02:06P but not HLA-A*02:05P alleles; and an ECOG performance status of 0 or 1...Participants will receive lymphodepletion chemotherapy (fludarabine 30 mg/m2/day for 4 days and cyclophosphamide 600 mg/m2/day for 3 days) followed by infusion of 1–10x109 ADP-A2M4CD8 T cells...Writing/editorial support was provided by Christine Ingleby, DPhil, CMPP, of Excel Scientific Solutions which was contracted and compensated by Adaptimmune. Previously presented at ESGO 2023, Istanbul, Türkiye."

Clinical • Combination therapy • IO biomarker • P2 data • Melanoma • Oncology • Ovarian Cancer • Solid Tumor • CD4 • CD8 • HLA-A • MAGEA4

First-line ADP-A2M4CD8 T-cell Receptor T-cell Therapy plus Pembrolizumab in Head and Neck Cancers: An Additional Cohort of the Phase 1 SURPASS Trial (MHNCS 2024) - P1 | "Lymphodepletion chemotherapy consisting of cyclophosphamide 600 mg/m 2 /day for 3 days and fludarabine 30 mg/m 2 /day for 4 days is administered, followed by ADP-A2M4CD8 infusion (1–10x10 9 transduced T cells). In a dedicated H&N cohort, participants will receive ADP-A2M4CD8 in combination with pembrolizumab in the first-line setting to evaluate the efficacy and safety of the combination. Study sponsor: Adaptimmune; writing/editing: Excel Scientific Solutions, funded by Adaptimmune."

Clinical • P1 data • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD4 • CD8 • HLA-A • MAGEA4 • PD-L1

ADP-A2M4CD8 as Monotherapy or in Combination With Either Nivolumab or Pembrolizumab in HLA-A2+ Subjects With MAGE-A4 Positive Tumors (SURPASS) (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Adaptimmune | Trial primary completion date: Sep 2023 ➔ Dec 2025

Combination therapy • Monotherapy • Trial primary completion date • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Urothelial Cancer • HLA-A • MAGEA4

New phase 1 SURPASS trial cohort: Early-line ADP-A2M4CD8 T-cell receptor T-cell therapy plus pembrolizumab in urothelial carcinoma. (ASCO-GU 2024) - P1 | " A dedicated UC cohort will enroll ≤15 pts with unresectable locally advanced or metastatic UC who have received first-line cisplatin-based standard-of-care (SOC) chemotherapy and are either currently receiving second-line SOC pembrolizumab or have received avelumab maintenance therapy and no second-line therapy...Pts receive lymphodepletion chemotherapy consisting of cyclophosphamide 600 mg/m2/day for 3 days and fludarabine 30 mg/m2/day for 4 days followed by ADP-A2M4CD8 infusion (1x109 to 10x109 transduced T-cells) and subsequent pembrolizumab 400 mg (administered every six weeks for ≤2 years, until unacceptable toxicity or disease progression)...Writing and editorial support was from Excel Scientific Solutions (Fairfield, CT, USA); funding was provided by Adaptimmune. Clinical trial information: NCT04044859."

New P1 trial • P1 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD4 • CD8 • HLA-A • MAGEA4

Clinical and translational data from the phase I SURPASS trial of ADP-A2M4CD8 T cell receptor (TCR) T cell therapy alone or combined with nivolumab in solid tumors (ESMO 2023) - P1 | "Nevertheless, inhibition of immunosuppressive pathways may improve anti-tumor responses; therefore, new SURPASS cohorts include ADP-A2M4CD8 combined with nivolumab or pembrolizumab. Data from additional pts treated by August 2023 will be presented. Conclusions ADP-A2M4CD8 continues to show an acceptable benefit-to-risk profile, including in pts receiving nivolumab combination therapy."

Clinical • IO biomarker • P1 data • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • MAGEA4

Next-Generation TCR T-cell Therapy (ADP-A2M4CD8) Demonstrates Strong Efficacy in a Broad Range of Solid Tumors; Adaptimmune Presents Data Update from its SURPASS trial at ESMO (Adaptimmune Press Release) - P1 | N=120 | SURPASS (NCT04044859) | Sponsor: Adaptimmune | "Adaptimmune Therapeutics plc...presented clinical and translational data from its Phase 1 SURPASS clinical trial (NCT04044859) investigating the next-generation engineered T-cell therapy ADP-A2M4CD8 at the Annual European Society for Medical Oncology (ESMO) Congress...Clinical data demonstrate efficacy signals supporting further development in ovarian, urothelial and head & neck cancers....As of the data cut-off, there were 46 evaluable patients who received ADP-A2M4CD8 monotherapy, and 10 who received ADP-A2M4CD8 in combination with nivolumab; In the 26 people in the monotherapy arm with ovarian, urothelial, and head & neck cancers, there were 13 clinical responses, resulting in a 50% response rate."

P1 data • Head and Neck Cancer • Ovarian Cancer • Urothelial Cancer

Next-Generation TCR T-cell Therapy (ADP-A2M4CD8) Demonstrates Strong Efficacy in a Broad Range of Solid Tumors; Adaptimmune Presents Data Update from its SURPASS trial at ESMO (Adaptimmune Press Release) - "Based on clear efficacy signals thus far in the Phase 1 SURPASS trial, we are eager to now focus on the head & neck and bladder cancer cohorts in earlier lines of treatment as well as the Phase 2 SURPASS-3 ovarian cancer trial...ADP-A2M4CD8 received FDA RMAT designation in 2022 for the treatment of patients with platinum resistant ovarian cancer and is currently enrolling....The trial is currently underway in collaboration with The GOG Foundation, Inc. (GOG) in the United States, with additional sites initiating in Canada, the United Kingdom, and the EU."

Trial status • Ovarian Cancer

A Phase 2 Study (GOG-3084) Of ADP-A2M4CD8 TCR T-Cell Therapy, Alone Or In Combination With Nivolumab, In Patients With Recurrent Ovarian Cancers (ESGO 2023) - P1, P2 | "Lymphodepletion chemotherapy (fludarabine 30 mg/m2/day for 4 days and cyclophosphamide 600 mg/m2/day for 3 days) will be followed by infusion of 1â10x10^9 ADP-A2M4CD8 T-cells. Adverse events will be monitored, with participants followed for 15 years from T-cell infusion. Conclusion SURPASS-3 is initiating in Q2 2023."

Clinical • Combination therapy • IO biomarker • P2 data • Melanoma • Oncology • Ovarian Cancer • Solid Tumor • CD4 • CD8 • HLA-A • MAGEA4

Adaptimmune Reports Second Quarter Financial Results and Business Update (Adaptimmune Press Release) - "Data from the completed pivotal clinical trial with lete-cel (IGNYTE-ESO) for the treatment of synovial sarcoma or myxoid/ round cell liposarcoma (MRCLS) is expected in late 2023. The transition of lete-cel to Adaptimmune from GSK is ongoing and terms were agreed during Q2 2023. The Company will determine next steps for lete-cel, including potential for a BLA, in early 2024....Initiated additional cohorts in the Phase 1 SURPASS trial in the earlier line treatment setting for head & neck and urothelial cancers in combination with checkpoint inhibitors. Data readouts anticipated in 2H 2024. An update on the Phase 1 SURPASS trial (ADP-A2M4CD8 alone or combined with nivolumab) will be featured as an oral presentation at the European Society of Medical Oncology (ESMO) 2023 Congress, Monday, October 23, 11:08-11:18 CET."

P1 data • P2 data • Genito-urinary Cancer • Head and Neck Cancer • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • Urothelial Cancer

ADP-A2M4CD8 Monotherapy and in Combination With Nivolumab in HLA-A2+ Subjects With MAGE-A4 Positive Ovarian Cancer (SURPASS-3) (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: Adaptimmune | Not yet recruiting ➔ Recruiting | Initiation date: Mar 2023 ➔ Jun 2023

Combination therapy • Enrollment open • Monotherapy • Trial initiation date • Oncology • Ovarian Cancer • Solid Tumor • BRCA • HLA-A • MAGEA4 • PARP1

ADP-A2M4CD8 in HLA-A2+ Subjects With MAGE-A4 Positive Esophageal or Esophagogastric Junction Cancers (SURPASS-2) (clinicaltrials.gov) - P2 | N=45 | Active, not recruiting | Sponsor: Adaptimmune | Trial primary completion date: Apr 2023 ➔ Dec 2023

Metastases • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • HLA-A • MAGEA4