product pipeline

product pipeline | publications & abstracts

TM-601

TM-601, or cholortoxin, is a synthetic polypeptide based on the amino acid sequences originally isolated from the venom of the scorpion Leiurus quinquestriatus (Figure 1).

Figure 1. Scorpion and 3-D Structure and Amino Acid Sequence of Chlorotoxin (TM-601).
Above, left: Giant Yellow Israeli scorpion which produces venom from which chlorotoxin peptide sequence was originally derived. Above, middle: 3-D structure of chlorotoxin determined by nuclear magnetic resonance (NMR). Above, right: Amino acid sequence of chlorotoxin.

TM-601 – Product Profile

Evidence of selective binding – In preclinical research, TM-601 has been shown to bind selectively with malignant cells of numerous tumor types, while showing a low affinity for normal healthy cells, as seen in the following slides (Figure 1).

Binding of TM-601 to Glioblastoma Cells

Figure 1A. No Peptide

Figure 1B. Non-specific Biotinylated Peptide

Figure 1C. Biotinylated TM-601

The following results demonstrate the tumor specificity of TM-601 in a variety of malignant and normal cells from human tissue samples (Table 1-A), and cultured cell samples (Table 1-B).

Table 1-A. Summary of Human Tissues Stained with TM-601

Table 1-B. Summary of Various Cultured Cells Stained with TM-601

Preclinical evidence of potential therapeutic effects
Preclinical studies with TM-601 in animal models have revealed a number of important findings that support the premise for therapeutic benefits in brain tumors:

Current clinical trial program

Transmolecular has developed a multi-tiered clinical research trial program to explore the potential of radio-labeled and unlabeled TM-601 in the treatment of high-grade glioma – a deadly form of brain cancer – and other aggressive cancers with limited treatment options.

Following the completion in 2004 of a phase I/II clinical trial to evaluate the safety of I-TM-601 administered through an intercavitary device to patients with glioblastoma, the company initiated a phase II trial under orphan, fast tract designation, to establish the efficacy, safety and tolerability of intercavitarily-administered, radio-labeled TM-601 for the same indication. With the dose-escalating stage of this study completed, the second, currently ongoing stage of the study is evaluating its effects on tumor progression and survival in 54 patients with high-grade glioma. Upon completion of the phase II study, Transmolecular plans to conduct a phase III trial to gain FDA approval to market I-TM-601 for treatment of recurrent, high-grade glioma in the United States.

Transmolecular is also conducting imaging studies of IV-administered I-TM-601 in patients with glioma and a variety of malignant/metastatic tumor types. The primary objective of these studies is to determine the efficacy of I-TM-601 in specifically localizing and interacting with tumor cells in patients when it is administered via IV infusion.

In addition, Transmolecular recently gained FDA approval of an IND to investigate unlabeled TM601 based on evidence that IV-administered, unlabeled TM-601 has antitumor effects of its own, potentially due to antiangiogenic activity. TransMolecular is planning to conduct a clinical study to evaluate the effects of unlabeled TM-601 alone in the treatment of high-grade glioma that is expected to begin enrolling patients in early 2008.

As the clinical study program for TM-601 moves forward, the company will continue with ongoing preclinical studies and research to determine the mechanism for the agent’s antitumor effects and to explore its potential as a diagnostic imaging tool for detecting primary and malignant tumors.

For more information on the clinical trial program for TM-601, click here.