BT7455 / Bicycle Therap - LARVOL DELTA

Multimodal targeting of Ephrin A2 in solid tumors using bi-cyclic drug conjugates (EACR 2025) - "The Bicycle Platform enables the development of a multimodal therapeutic approach for solid tumor treatment, including the targeting of previously intractable proteins for other agents such as ADCs, therefore offering the opportunity to develop both best and first in class therapies. This approach is exemplified herein with EphA2 targeting Bicycle® containing molecules, with BT5528 currently in Phase 1/2 clinical trials"

Oncology • Solid Tumor • EPHA2 • TNFRSF9

Tumor-targeted activation of CD137 using Bicycles: New insights into mechanism of action and discovery of BT7455, a clinical candidate for the treatment of EphA2-expressing cancers (AACR 2024) - "In summary, we have identified EphA2 as a promising target to pair with a CD137 agonist. In addition to CD8+ T cells, tumor-resident dendritic cells are a likely contributor to anti-tumor immunity following treatment with Bicycle® TICAs, supporting utility for Bicycle® tumor-targeted CD137 agonists in solid tumors beyond those that are highly T cell-infiltrated. We have advanced a clinical development candidate, BT7455, to realize this potential for patients with EphA2-expressing cancers."

Clinical • IO biomarker • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • EPHA2 • TNFRSF9

Bicycle Therapeutics to Present at the AACR Annual Meeting 2024 (Businesswire) - "Bicycle Therapeutics plc...announced the acceptance of three abstracts for poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2024, taking place in San Diego on April 5-10."

Preclinical • Oncology

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

Bicycle Therapeutics to Present Four Posters Highlighting Preclinical Data from its Bicycle Tumor-Targeted Immune Cell Agonist (Bicycle TICA) Programs at the SITC 36th Annual Meeting (Yahoo Finance) - “Bicycle Therapeutics plc…today 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 four poster presentations at the Society for Immunotherapy of Cancer’s (SITC) 36th Annual Meeting, being held in Washington D.C. and virtually on November 10-14, 2021….Preclinical results that will be presented at SITC support Bicycle’s decision to initiate a Phase I/II clinical trial of BT7480…Bicycle found that plasma and tumor drug concentration levels may be associated with tumor growth inhibition. EphA2/CD137 Bicycle TICA results in syngeneic mouse tumor models produced complete anti-tumor responses in vivo. These results reveal that costimulatory molecules that exploit intermittent rather than continuous exposure may promote optimal anti-tumor activity.”

Preclinical • Oncology

Bicycle Therapeutics Announces Publication of Article Highlighting Preclinical Data of Tumor-Targeted Immune Cell Agonists (TICAs) in the Journal for ImmunoTherapy of Cancer (Businesswire) - “Results showed that by linking a costimulatory receptor (e.g., CD137) targeting Bicycle to a tumor antigen (e.g., EphA2), targeting Bicycle potent agonists were created, which activated the costimulatory receptor selectively in the presence of tumor cells expressing that antigen. An EphA2/CD137 TICA efficiently co-stimulated human peripheral blood mononuclear cells in vitro in the presence of EphA2-expressing tumor cell lines, as measured by an increased secretion of interferon γ and interleukin-2.”

Preclinical • Oncology

Bicycle Therapeutics Presents Posters at the SITC 35th Anniversary Annual Meeting (Businesswire) - ‘“we look forward to initiating a clinical trial for our lead IO program, BT7480, in 2021’…This finding supports potential dosing of BT7480 in combination with checkpoint inhibitors. At dose levels tested, BT7480 has been shown to be well-tolerated in non-human primates. IND-enabling activities for BT7480 are ongoing….EphA2/CD137 TICAs demonstrated potent EphA2-dependent activity in both CD137 reporter and primary immune cell assays…There, complete responder animals became resistant to rechallenge with MC38 tumor cells, implying an immunogenic memory response. Bicycle also showed a potential ability to induce significant modulation of the tumor immune microenvironment, including immune checkpoints. Bicycle announced earlier this year that it has selected an EphA2/CD137 TICA candidate, BT7455.”

IND • Preclinical • Oncology

Bicycle Therapeutics Announces Gross Proceeds of $50.0 Million from its At-the-Market Offering Program and Enters into Debt Financing from Hercules Capital (Bicycle Therapeutics Press Release) - "Bicycle plans to use the proceeds of the financings to advance its oncology pipeline of Bicycle Toxin Conjugates and immuno-oncology candidates through multiple clinical milestones expected in 2021, including interim updates from the ongoing Phase IIa trial of BT1718, Phase I/II trial of BT5528 and Phase I/II trial of BT8009, as well as the initiation of a Phase I/II trial of BT7480 and advancement of IND-enabling studies for BT7455."

New P1/2 trial • Preclinical • Trial status • Oncology

Bicycle Therapeutics to present new translational research for BT5528 and preclinical data for tumor-targeted immune cell agonists at the AACR Virtual Annual Meeting II (Businesswire) - "Bicycle Therapeutics plc…announced that new translational research for second-generation Bicycle® Toxin Conjugate (BTC) BT5528 and preclinical data for novel, fully synthetic tumor-targeted immune cell agonists (TICAs™) BT7480 and BT7455 will be presented during poster sessions at the American Association for Cancer Research (AACR) Virtual Annual Meeting II on June 22-24, 2020. All e-posters will be made available for browsing on AACR’s e-poster website starting June 22."

Clinical data • Preclinical • Oncology