Pharmacokinetic (PK) assessment of BT1718: A phase I/II a study of BT1718, a first in class bicycle toxin conjugate (BTC), in patients (pts) with advanced solid tumours

Cook, Natalie; Banerji, Udai; Evans, Jeff; Biondo, Andrea; Germetaki, Theodora; Randhawa, Manreet; Godfrey, Lisa; Leslie, S.; Jeffrey, Phil; Rigby, Michael; Bennett, Gavin; Blakemore, Stephen J.; Koehler, Maria; Niewiarowski, Andrew; Pittman, Marc; Symeonides, Stefan N.

doi:10.1093/annonc/mdz244.026

Cited by 13 publications

(7 citation statements)

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“…BT1718 is a bicycle drug conjugate with antitumor activity developed by Bicycle Therapeutics. This conjugate is composed of a 13–amino acids bicyclic peptide covalently linked to a toxin (DM1), a potent anti-tubulin agent [ 146 , 147 ]. The peptide part of this conjugate binds with high affinity and specificity to membrane type I matrix metalloproteinase (MT1-MMP) [ 147 ].…”

Section: Cyclic Peptides In the Pipelinementioning

confidence: 99%

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Cyclic Peptides in Pipeline: What Future for These Great Molecules?

2023

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Cyclic peptides are molecules that are already used as drugs in therapies approved for various pharmacological activities, for example, as antibiotics, antifungals, anticancer, and immunosuppressants. Interest in these molecules has been growing due to the improved pharmacokinetic and pharmacodynamic properties of the cyclic structure over linear peptides and by the evolution of chemical synthesis, computational, and in vitro methods. To date, 53 cyclic peptides have been approved by different regulatory authorities, and many others are in clinical trials for a wide diversity of conditions. In this review, the potential of cyclic peptides is presented, and general aspects of their synthesis and development are discussed. Furthermore, an overview of already approved cyclic peptides is also given, and the cyclic peptides in clinical trials are summarized.

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Section: Cyclic Peptides In the Pipelinementioning

confidence: 99%

“…BT1718 is currently in phase I/IIa clinical trial in which the maximum safe dose, the potential side effects, and pharmacokinetic properties in patients with advanced solid tumors are being studied (ClinicalTrials.gov Identifier: NCT03486730) [ 146 ].…”

Section: Cyclic Peptides In the Pipelinementioning

confidence: 99%

Cyclic Peptides in Pipeline: What Future for These Great Molecules?

2023

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“…EP-100 and BT1718 had entered phase II clinical trial for the treatment of ovarian cancer and breast cancer or the advanced solid tumors with high MT-1 expression, respectively. [10][11][12] Transferrin receptor (TfR) is a hopeful target in cancer therapy due to its overexpress on the surface of most solid tumors. TfR belongs to type II transmembrane glycoprotein with a special extracellular structure.…”

Section: Introductionmentioning

confidence: 99%

LWJ-M30, a conjugate of DM1 and B6, for the targeted therapy of colorectal cancer with improved therapeutic effects

Zhang¹,

Yu²,

Luan³

et al. 2023

RSC Adv.

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“…1 Two previously reported BTCs, namely, BT1718 and BT5528 (Figure 1), which target MT1-MMP and EphA2, respectively, show potent anticancer activity in preclinical studies 1,3 and are currently being assessed in the clinic, 6 with preliminary clinical pharmacokinetic (PK) results for BT1718 demonstrating concentrations of payload in tumors are similar to those observed in preclinical rodent models. 2 We have now sought to employ BTCs against additional cancer targets, including Nectin-4.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Bicycle toxin conjugates (BTCs) are a new class of anticancer agents that allow efficient and targeted delivery of toxin payloads into tumors. − They consist of a highly constrained, tumor-targeting synthetic bicyclic peptide that is conjugated to a cytotoxic payload via a cleavable linker, which allows payload release in the tumor microenvironment. , …”

Section: Introductionmentioning

confidence: 99%

Discovery of BT8009: A Nectin-4 Targeting Bicycle Toxin Conjugate for the Treatment of Cancer

et al. 2022

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Bicycle toxin conjugates (BTCs) are a promising new class of molecules for targeted delivery of toxin payloads into tumors. Herein we describe the discovery of BT8009, a Nectin-4 targeting BTC currently under clinical evaluation. Nectin-4 is overexpressed in multiple tumor types and is a clinically validated target for selective delivery of cytotoxic payloads. A Nectin-4 targeting bicyclic peptide was identified by phage display, which showed highly selective binding for Nectin-4 but suffered from low plasma stability and poor physicochemical properties. Multiparameter chemical optimization involving introduction of non-natural amino acids resulted in a lead Bicycle that demonstrated high affinity for Nectin-4, good stability in biological matrices, and a much-improved physicochemical profile. The optimized Bicycle was conjugated to the cytotoxin Monomethyl auristatin E via a cleavable linker to give the targeted drug conjugate BT8009, which demonstrates potent anticancer activity in in vivo rodent models.

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Pharmacokinetic (PK) assessment of BT1718: A phase I/II a study of BT1718, a first in class bicycle toxin conjugate (BTC), in patients (pts) with advanced solid tumours

Cited by 13 publications

References 0 publications

Cyclic Peptides in Pipeline: What Future for These Great Molecules?

Cyclic Peptides in Pipeline: What Future for These Great Molecules?

LWJ-M30, a conjugate of DM1 and B6, for the targeted therapy of colorectal cancer with improved therapeutic effects

Discovery of BT8009: A Nectin-4 Targeting Bicycle Toxin Conjugate for the Treatment of Cancer

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