BT7480 / Bicycle Therap - LARVOL DELTA

Phase 1/2 study of BT7480, a CD137/Nectin-4 Bicycle tumor-targeted immune cell agonist (TICA) with nivolumab (nivo) in Nectin-4–associated advanced solid tumors (ESMO 2026) - No abstract available

Immune cell • Metastases • P1/2 data • Oncology • Solid Tumor • NECTIN4 • TNFRSF9

Bicycle Continued Access Protocol (BiCAP) for Participants Receiving a Bicycle Investigational Product (clinicaltrials.gov) - P2 | N=16 | Not yet recruiting | Sponsor: BicycleTx Limited

New P2 trial • Oncology • Solid Tumor

BT7480, a Bicycle tumor-targeted immune cell agonist… (Businesswire) - "Phase 1 BT7480 combination data with nivolumab will be presented at a scientific conference in the first half of 2026. After reporting combination data, Bicycle Therapeutics will no longer develop BT7480 internally and intends to seek a potential partner for future development."

Licensing / partnership • P1 data • Pipeline update • Solid Tumor

Study BT7480-100 in Patients With Advanced Malignancies Associated With Nectin-4 Expression (clinicaltrials.gov) - P1/2 | N=200 | Active, not recruiting | Sponsor: BicycleTx Limited | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Sep 2025 ➔ Aug 2026

First-in-human • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • NECTIN4

Bicycle Therapeutics Highlights…Strategic Priorities for 2026 (Businesswire) - "...Anticipated Milestones:...(i) Report additional Phase 1 Duravelo-1 combination data with pembrolizumab in first-line cisplatin-ineligible mUC at a scientific conference in the first half of 2026; (ii) Report longer-term follow-up Phase 1 Duravelo-1 monotherapy data in late-line mUC at a scientific conference in the first half of 2026; (iii) Report Phase 1 BT7480 combination data with nivolumab at a scientific conference in the first half of 2026."

P1 data • Urothelial Cancer

Phase 1 BT7480 combination data with nivolumab will now be presented at scientific conference in the first half of 2026. (Businesswire)

P1 data • Solid Tumor

Study BT7480-100 in Patients With Advanced Malignancies Associated With Nectin-4 Expression (clinicaltrials.gov) - P1/2 | N=200 | Active, not recruiting | Sponsor: BicycleTx Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • NECTIN4

Bicycle Therapeutics…Highlights 2025 Strategic Priorities and Milestones (Businesswire) - "2025 Strategic Priorities and Anticipated Milestones:...Advance targeted therapeutics pipeline addressing novel targets that have historically been challenging to treat: (i) Report Phase 1 combination data for BT5528 plus nivolumab in 4Q 2025; (ii) Report Phase 1 combination data for BT7480 plus nivolumab in 4Q 2025."

P1 data • Solid Tumor

Mechanistic biomarker analyses following administration of BT7480, a novel Nectin-4/CD137 bicycle tumor-targeted immune cell agonist®, in a phase 1/2 study in patients with advanced solid tumors (SITC 2024) - P1/2 | "Simultaneous binding of Nectin-4 and CD137 induces complete tumor regression and resistance to tumor re-challenge in preclinical models.1 A phase 1/2 study (NCT05163041) is evaluating BT7480 ± nivolumab in patients with Nectin-4 associated advanced solid tumors. These data support the continued development of BT7480 in patients with Nectin-4 associated solid tumors, with the potential for future clinical use in combination with checkpoint inhibitors. Ethics Approval The protocol was approved by the independent ethics committees and institutional review boards of the participating centers."

Biomarker • Clinical • Immune cell • IO biomarker • Metastases • P1/2 data • Cervical Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CXCL9 • NECTIN4 • TNFRSF9

Initial results from a phase I/II study of BT7480, a novel nectin-4/CD137 bicycle tumor-targeted immune cell agonist, in patients (pts) with advanced solid tumors (ESMO 2024) - P1/2 | "This phase 1/2 study (NCT05163041) will evaluate BT7480 ± nivolumab in pts with cancer. BT7480 was well tolerated and showed antitumor activity in pts with advanced Nectin-4–associated solid tumors. Biomarker analyses suggest BT7480 dual targeting of CD137 and Nectin-4 enhanced immune activation; PD activity was consistent with the BT7480 mechanism of action."

Clinical • Immune cell • IO biomarker • Metastases • P1/2 data • Anal Carcinoma • Cervical Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD4 • CXCL9 • NECTIN4 • TNFRSF9

Bicycle Therapeutics Presents Updated Clinical Results Across Oncology Pipeline at ESMO Congress 2024 (Businesswire) - P1/2 | N=200 | NCT05163041 | Sponsor: BicycleTx Limited | "Initial data from the Phase 1/2 dose escalation trial evaluating BT7480 in patients with advanced solid tumors showed:...Among 39 patients assigned to receive one of 10 different doses (0.002-3.5 mg/kg weekly) of BT7480, an emerging differentiated safety and tolerability profile with a low number of severe adverse events; Best overall response of stable disease in 13 patients, 5 of whom had NSCLC. Stable disease was prolonged (>8 months) in 3 patients, 2 with NSCLC and 1 with anal cancer; Preliminary biomarker analyses that support BT7480 dual targeting of CD137 and Nectin-4 as demonstrated by enhanced immune cell activation, aligned with the proposed mechanism of action of BT7480."

P1/2 data • Non Small Cell Lung Cancer • Solid Tumor

Bicycle Therapeutics Reports Recent Business Progress and Second Quarter 2024 Financial Results (Businesswire) - "Four abstracts accepted for poster presentation at the European Society for Medical Oncology (ESMO) Congress 2024 being held September 13-17 in Barcelona. Bicycle Therapeutics will present four abstracts containing updated clinical data for zelenectide pevedotin (formerly BT8009) in metastatic urothelial cancer (mUC), BT5528 in advanced solid tumors such as mUC and ovarian, and BT7480 in advanced solid tumors."

Clinical data • Genito-urinary Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • Urothelial Cancer

Bicycle Therapeutics Announces Four Abstracts Accepted for Presentation at the ESMO Congress 2024 (Businesswire) - "Bicycle Therapeutics plc...announced the acceptance of four abstracts for poster presentation at the European Society for Medical Oncology (ESMO) Congress 2024, taking place September 13-17 in Barcelona."

P1/2 data • Gastrointestinal Cancer • Head and Neck Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer

Bicycle Therapeutics Reports Recent Business Progress and First Quarter 2024 Financial Results (Businesswire) - "Continued progress across research and development (R&D) pipeline, with numerous clinical data readouts and program updates expected in 2H 2024. Importantly, Bicycle Therapeutics initiated the Phase 2/3 Duravelo-2 registrational trial for BT8009 in mUC, and patient enrollment is ongoing. The company continues to assess BT8009, BT5528 and BT7480 in Phase 1/2 clinical trials across a variety of tumor types, and plans to provide updates from its wholly owned Bicycle Radio Conjugate (BRC) pipeline."

Clinical data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Bicycle Therapeutics Reports Recent Business Progress and Fourth Quarter and Full Year 2023 Financial Results (Businesswire) - "Execute plan to become a leader in next-generation solid tumor therapeutics and combinations, which includes: Initiating the Phase 2/3 Duravelo-2 registrational trial for BT8009 in metastatic urothelial cancer (mUC) in 1Q 2024. The trial is now active and recruiting patients. Conducting further clinical studies to assess BT8009, BT7480 and BT5528 in emerging tumors of interest, with data from these studies expected in 2H 2024. Expand opportunities in oncology, which includes: Advancing the company’s next generation of Bicycle Toxin Conjugates (BTCs). The company plans to select a BTC clinical candidate using next-generation technology in 2H 2024. Validating the company’s Bicycle Radio Conjugates (BRC) pipeline and partner for success, with updates expected from its wholly owned BRC program by mid-2024."

Clinical data • New molecule • Trial status • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Bicycle Therapeutics Provides Data Updates for Three Clinical Programs and Strategy Overview at First R&D Day (Businesswire) - P1/2 | N=200 | NCT05163041 | Sponsor: BicycleTx Limited | "In 33 patients assigned to receive one of 9 different doses of BT7480, an emerging differentiated safety and tolerability profile with a low number of severe adverse events. The majority of the patients studied had tumors that expressed Nectin-4 and CD137. Two unconfirmed partial responses in heavily pre-treated patients with cervical cancer. Three prolonged stable disease (≥7 months) in NSCLC and anal cancer. Bicycle Therapeutics will continue to define the recommended Phase 2 dose (or maximum dose) and dose range for BT7480, with a view to enroll combination cohorts with checkpoint inhibitors in 2024. These data will inform the design of a Phase 2 trial that could support potential accelerated approval of BT7480."

P1/2 data • Trial status • Anal Carcinoma • Cervical Cancer • Non Small Cell Lung Cancer

Bicycle Therapeutics Reports Second Quarter 2023 Financial Results and Provides Corporate Update (Businesswire) - "Research and development expenses were $39.7 million for the three months ended June 30, 2023, compared to $19.9 million for the three months ended June 30, 2022. The increase in expense of $19.9 million was primarily due to increased clinical program expenses for BT8009, BT7480 development expenses, and other discovery and platform related expenses, as well as increased personnel-related expenses, including incremental non-cash share-based compensation expense of $1.3 million, offset by incremental UK research and development incentives."

Commercial • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Triple Negative Breast Cancer • Urothelial Cancer

Phase 1/2 study of the safety, pharmacokinetics, and preliminary clinical activity of BT7480 in patients with nectin-4 associated advanced malignancies (AACR 2023) - P1/2 | "PK and PD analyses will be performed to support dose escalation decisions and to further the understanding of safety and clinical activity signals as a result of treatment with BT7480. This study is actively recruiting."

Clinical • IO biomarker • Metastases • P1/2 data • PK/PD data • Oncology • Solid Tumor • NECTIN4 • TNFRSF9

EphA2-dependent CD137 agonism and anti-tumor efficacy by BT7455, a Bicycle tumor-targeted immune cell agonist® (AACR 2023) - "The first molecule of this class, BT7480, a Nectin-4-dependent CD137 (4-1BB) agonist, entered clinical trials in 2021 in patients with solid tumors associated with Nectin-4 expression...The kinetics and extent of the immune microenvironment modulation differentiated BT7455 from both a checkpoint inhibitor (anti-mouse PD-1) as well as an anti-CD137 agonist antibody (urelumab analogue)...Cancer Res 2020; 80:5300 4Xiao, et al. J Hematol Oncol 2020; 13:114."

Clinical • Immune cell • IO biomarker • Oncology • Solid Tumor • CD8 • IFNG • IL2 • NECTIN4 • TNFRSF9

Bicycle Therapeutics to Present at the 2023 AACR Annual Meeting (Businesswire) - "Bicycle Therapeutics plc...announced that the company will present four poster presentations at the 2023 American Association for Cancer Research (AACR) Annual Meeting, taking place in Orlando, FL on April 14-19, 2023."

Preclinical • Trial status • Oncology • Solid Tumor

Bicycle Therapeutics to Present Five Posters Highlighting Preclinical Data from its Bicycle Tumor-Targeted Immune Cell Agonist (Bicycle TICA) Programs at the SITC 37th Annual Meeting (Businesswire) - "Bicycle Therapeutics plc...announced that preclinical data for BT7480, a novel Bicycle tumor-targeted immune cell agonist (Bicycle TICA), and BT7455, an EphA2/CD137 Bicycle TICA, will be presented in five poster presentations at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting, being held in Boston, M.A. and virtually on November 8-12, 2022."

Preclinical • Oncology

Transcriptional profiling of Bicycle tumor-targeted CD137 agonist-treated mouse tumors revealed an early and rapid activation of myeloid cells followed by infiltration of cytotoxic T cells into the tumor (SITC 2022) - "Conclusions Altogether, these data highlight that CD137 Bicycle ® TICAs like BT7480 and BT7455 impact immune cell populations beyond T cells. This suggests that abundant T cell infiltrates may not be required for Bicycle ® CD137 agonists to initiate tumor rejection, which broadens the patient population that may benefit from CD137 Bicycle TICA™ treatment to also include myeloid-rich tumors with lower T cell infiltration (“colder” tumors)."

IO biomarker • Preclinical • Oncology • CCL2 • CCL22 • CD8 • ITGAM • NECTIN4

BT7455, a fully synthetic Bicycle tumor-targeted immune cell agonist, leads to potent EphA2-dependent CD137 agonism and robust anti-tumor efficacy (SITC 2022) - "1 The first molecule of this class, BT7480, a Nectin-4-dependent CD137 (4-1BB) agonist, entered clinical trials in 2021 in patients with solid tumors associated with Nectin-4 expression...The kinetics and extent of the immune microenvironment modulation differentiated BT7455 from both a checkpoint inhibitor (anti-mouse PD-1) as well as an anti-CD137 agonist antibody (Urelumab analogue)...Conclusions BT7455 is a highly potent EphA2 expression-dependent CD137 agonist with optimal target binding, pharmacologic, and pharmacokinetic properties that enable intermittent dosing for curative effect through modulation of the tumor immune microenvironment in syngeneic mouse models. BT7455 is currently being evaluated in IND-enabling safety studies."

Clinical • IO biomarker • Oncology • Solid Tumor • EPHA2 • IFNG • IL2 • NECTIN4 • TNFRSF9

A combined phase I/II study of a novel bicycle tumor-targeted immune cell agonist BT7480 in patients with nectin-4 associated advanced malignancies. (ASCO 2022) - P1/2 | "Cohorts 1 and 2 have been completed without DLT. Enrollment in cohort 3 began in January 2022."

Clinical • IO biomarker • P1/2 data • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Disorders • Hypertension • Immune Modulation • Immunology • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • NECTIN4 • TNFRSF9

Bicycle Therapeutics Reports Third Quarter 2022 Financial Results and Provides Corporate Update (Businesswire) - "'In the third quarter, we announced top-line results from the completed dose escalation portion of the Phase I/II trial in BT5528 and expect to complete enrollment in the initial expansion cohorts this quarter. In addition, clinical development of BT8009 remains on-track and we look forward to providing an update this quarter following completion of the dose escalation portion of the Phase I/II clinical trial. Finally, the dose escalation portion of our Phase I/II trial of BT7480 continues at a healthy pace and we expect to share clinical information in 2023'."

Enrollment status • P1/2 data • Oncology • Solid Tumor