TLN-232 (Formerly CAP-232)
TLN-232 is a novel seven amino-acid peptide under development targeting solid tumours. It targets pyruvate kinase M2 (M2PK), a protein shown to be over-expressed in a number of different tumour types. M2PK is involved in tumour cell glycolysis, a process by which cancer cells generate the energy required for their rapid growth in the absence of oxygen.
Extensive preclinical studies have demonstrated the tumour-killing properties of TLN-232 in a variety of biological and animal models. In vivo animal studies have confirmed TLN-232 is efficacious against pancreatic, melanoma, liver, sarcoma and a variety of other cancers.
TLN-232 has completed two Phase I trials in healthy volunteers and one open-label Phase II trial in late-stage metastatic melanoma patients refractory to other anti-cancer treatments. The first Phase I was a dose escalation trial involving 16 patients that received TLN-232 or placebo administered on a weekly basis. No maximum tolerated dose was attained. TLN-232 was found to be safe, non-toxic and the treatment was not associated with any serious adverse events. In the second Phase I trial the highest dose from the previous study, 480 µg/kg, was administered to 10 patients as a four-hour daily intravenous infusion over a 10-day period. No drug-related serious adverse events were reported. The Phase II trial involved 13 metastatic melanoma patients that who received four treatment cycles involving four-hour intravenous infusions of TLN-232 at 480 µg/kg/day over seven consecutive days followed by a seven day wash-out period. The drug was safe and well tolerated with no clinically-significant toxicity or drug-related serious adverse events. TLN-232 achieved a 31% response rate, including three patients with stable disease and one patient who experienced a partial response.
In February 2008, the Company announced that it had completed patient enrollment for the Phase II trial of TLN-232 in refractory renal cell carcinoma patients. The open label trial was designed to assess the safety and pharmacokinetic profile of Thallion's new continuous intravenous formulation of TLN-232, as well as provide efficacy data in patients who had failed to benefit from the current standard of care. The trial was designed to administer 0.48 mg/kg/day of TLN-232 through continuous intravenous infusion for three cycles, each cycle consisting of 21 days of treatment followed by seven days of rest.
Thallion intends to initially develop TLN-232 for three primary applications; renal cell carcinoma, metastatic melanoma and pancreatic cancer. Almost 32,000 cases of renal cell carcinoma are diagnosed annually in the U.S. resulting in approximately 12,000 deaths. Metastatic melanoma affects approximately 41,000 people each year worldwide, including 8,000 in the U.S. Meanwhile, over 37,000 cases of pancreatic cancer are diagnosed each year in the U.S leading to 33,000 deaths annually from the disease.