Bicycle Toxin Conjugates Clinical Trials Bicycle Toxin Conjugate Research Bicycle Therapeutics Clinical Pipeline Report Insight

Release Date: 07-Feb-2024

Bicycle toxin conjugates are a promising advancement in targeted cancer treatment. They use bicyclic peptides to deliver toxic payloads to cancer cells. This method seeks to address the limitations of current targeted medicines, such as antibody-drug conjugates. In bicycle toxin conjugates, a bicyclic peptide attaches to a cancer cell target and transports a chemically coupled cell-killing toxin. The toxin is secreted inside cancer cells while preserving healthy tissue. Bicycle toxin conjugates have benefits over antibody-drug conjugates, another drug class with a similar action, due to the features of bicyclic peptides. Their small size allows them to penetrate tumors more effectively than bulky antibodies. Moreover, bicyclic peptides have better affinity and selectivity for their targets.


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Bicycle Therapeutics is actively spearheading the research of bicycle toxin conjugates. Early clinical data for the company’s cycling toxin conjugate compounds show promising anticancer efficacy against a variety of malignancies. Bicycle Therapeutics’ bicycle toxin compound, BT8009, which targets Nectin-4, has decreased tumors in bladder cancer. BT1718, another bicycle toxin combination created by Bicycle Therapeutics, which targets membrane type 1-matrix metalloproteinase (MT1-MMP), showed tumor reduction in phase 1/2 trials for solid tumors. Furthermore, BT5528, which targets Ephrin type-A receptor 2 (EphA2), is being studied in a phase 1/2 trial for urothelial cancer, ovarian cancer, triple negative breast cancer, and non-small cell lung cancer, among other cancers.


Bicycle toxin conjugates have the potential to supplement conventional cancer treatments like as antibodies and targeted medicines. Their bicyclic peptide delivery technique allows them to hit targets that lack good antibody binders. Smaller build sizes could also result in faster clinical development. Bicycle toxin conjugates may allow for lower overall drug dosages than antibodies, hence lowering systemic toxicity.


As more bicycle toxin conjugate candidates progress through clinical trials, there is optimism for identifying the best bicyclic peptide binders, linkers, and payloads for various cancer types. Bicycle Therapeutics’ first generation bicycle toxin conjugates currently have a DM1 payload attached to the peptide via a hindered disulphide cleavable linker, whereas their second-generation bicycle toxin conjugates have a valine-citrulline, or val-cit, cleavable linker attached to an MMAE payload. Next generation bicycle toxin conjugates are also being developed to have better properties than existing candidates.


Bicycle toxin conjugates have the potential to significantly affect cancer treatment by broadening the number of druggable targets and enhancing the therapeutic window when compared to existing biologics. While still in early stages of development, their clinical promise underlines the importance of ongoing research and optimization of bicycle toxin conjugates as precision cancer treatments.

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