Future Clinical Development Plans Outlined for Tekmira’s Oncology Therapeutic, TKM-PLK1
VANCOUVER, Canada I August 12, 2013 I Tekmira Pharmaceuticals Corporation (TKMR) (TKM.TO), a leading developer of RNA interference (RNAi) therapeutics, today announced that it has initiated a Phase I/II clinical trial with TKM-PLK1, its RNAi oncology therapeutic for the treatment of solid tumors.
“We are excited today to outline our broad development plans for TKM-PLK1. Based on the encouraging results from our Phase I clinical trial, we are initiating a Phase I/II clinical trial with TKM-PLK1, which will enroll patients with either advanced Gastrointestinal Neuroendocrine Tumors (GI-NET) or Adrenocortical Carcinoma (ACC). By focusing on these indications, where we observed drug activity in the Phase I trial, we aim to collect additional data on the efficacy of TKM-PLK1 to guide our future development and regulatory strategy for this promising agent. We expect to have results from this completed trial by mid-2014, and if supported by the data, commence a pivotal trial in GI-NET in 2014. In addition, we anticipate initiating a separate Phase I/II clinical trial with TKM-PLK1, which will enroll patients with Hepatocellular Carcinoma (HCC) in the first half of 2014,” said Dr. Mark J. Murray, Tekmira’s President and CEO.
The GI-NET and ACC Phase I/II clinical trial will be a multi-center, single arm, open label study designed to measure efficacy using RECIST and tumor biomarkers for GI-NET patients, as well as to evaluate the safety, tolerability and pharmacokinetics of TKM-PLK1. TKM-PLK1 will be administered weekly with each four-week cycle consisting of three once-weekly doses followed by a rest week. It is expected that approximately 20 patients with advanced GI-NET or ACC tumors will be enrolled in this trial, with a minimum of 10 GI-NET patients to be enrolled.
Tekmira will also initiate another Phase I/II clinical trial with TKM-PLK1, enrolling patients with Hepatocellular Carcinoma (HCC) in the first half of 2014. This clinical trial will be a multi-center, open label, non-randomized, dose escalation study designed to evaluate the safety, tolerability and pharmacokinetics of TKM-PLK1 as well as determine the maximum tolerated dose in HCC patients and measure the anti-tumor activity of TKM-PLK1 in HCC patients.
“Tekmira has completed its Phase I expansion cohort study examining safety of the established maximum tolerated dose (MTD) for TKM-PLK1 in advanced solid tumors. In the expansion cohort, TKM-PLK1 has been administered to a total of 12 patients. To date, four patients are evaluable for efficacy, having received two cycles of TKM-PLK1. Of those four patients, one patient with ACC achieved stable disease. No GI-NET patients were enrolled in this expansion cohort. Thus, we are looking forward to focusing on patients with GI-NET or ACC tumors in this newly initiated trial,” added Dr. Murray.
About TKM-PLK1
Tekmira’s lead oncology product candidate, TKM-PLK1, targets polo-like kinase 1 (PLK1), a protein involved in tumor cell proliferation and a validated oncology target. Inhibition of PLK1 expression prevents the tumor cell from completing cell division, resulting in cell cycle arrest and death of the cancer cell. PLK1 has been a target of interest for years, and evidence that patients with elevated levels of PLK1 in their tumors exhibit poorer prognosis and survival rates has been documented in the medical literature. By using an RNAi approach and exploiting its naturally occurring mechanism of action, Tekmira can potentially overcome the limitations of other approaches and effectively silence PLK1.
In April 2013, results from the dose escalation portion of a Phase I clinical trial were presented at the 2013 American Association for Cancer Research (AACR) Annual Meeting. TKM-PLK1, which employs a unique lipid nanoparticle (LNP) formulation for oncology applications, was administered to 24 patients at doses ranging from 0.15 mg/kg to 0.90 mg/kg; with a total of 152 doses administered and a mean number of 6.2 doses per patient (range of 1-31 doses). Based on these data, the maximum tolerated dose is estimated to be 0.75 mg/kg. Forty-four percent (4 out of 9) of patients evaluable for response, treated at a dose equal to or greater than 0.6 mg/kg, showed clinical benefit. In particular, one patient with progressive, metastatic appendiceal carcinoid (neuroendocrine) cancer had a durable partial tumor response based on RECIST criteria, continuing for more than 10 months. Three other patients achieved stable disease, including one patient with metastatic appendiceal carcinoid (neuroendocrine) cancer, another patient with metastatic colorectal cancer, and a third patient with metastatic adrenocortical carcinoma.
About Gastrointestinal Neuroendocrine Tumors (GI-NET)
Neuroendocrine tumors (NETs) refers to a group of unusual and complex cancers that affect neuroendocrine cells, with those arising in the gastrointestinal tract referred to as GI-NET. It is estimated that there has been a four-fold increase in the incidence of NETs between 1973 and 2004. Approximately 55,000 people are living with GI-NET in the United States. There is a poor prognosis for advanced metastatic NETs, with 25% of patients surviving less than one year. The treatment of patients with gastrointestinal neuroendocrine tumors remains a challenge, and currently there are no approved drugs or treatments indicated specifically for GI-NET.
About Adrenocortical Carcinoma (ACC)
Adrenocortical Carcinoma (ACC) is a rare cancer that forms in the outer layer of tissue of the adrenal gland (a small organ on top of each kidney that makes steroid hormones, adrenaline, and noradrenaline to control heart rate, blood pressure, and other body functions). Even with appropriated diagnosis and treatment, most patients will develop recurrence and succumb to ACC because of the underlying tumor biology, the difficulty of achieving a complete resection, and the lack of effective systemic therapies.
About Hepatocellular Carcinoma (HCC)
Primary liver cancer, or hepatocellular carcinoma (HCC), is one of the most common cancers worldwide, with more than 630,000 people diagnosed each year. HCC represents a major unmet medical need and is associated with one of the poorest survival rates in oncology, in part because only 10-20% of hepatocellular carcinomas can be removed completely using surgery.
About RNAi and Tekmira’s LNP
RNAi therapeutics have the potential to treat a broad number of human diseases by “silencing” disease causing genes. The discoverers of RNAi, a gene silencing mechanism used by all cells, were awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi therapeutics, such as “siRNAs,” require delivery technology to be effective systemically. Tekmira believes its LNP technology represents the most widely adopted delivery technology for the systemic delivery of RNAi therapeutics. Tekmira’s LNP platform is being utilized in multiple clinical trials by both Tekmira and its partners. Tekmira’s LNP technology (formerly referred to as stable nucleic acid-lipid particles or SNALP) encapsulates siRNAs with high efficiency in uniform lipid nanoparticles that are effective in delivering RNAi therapeutics to disease sites in numerous preclinical models. Tekmira’s LNP formulations are manufactured by a proprietary method which is robust, scalable and highly reproducible, and LNP-based products have been reviewed by multiple FDA divisions for use in clinical trials. LNP formulations comprise several lipid components that can be adjusted to suit the specific application.
About Tekmira
Tekmira Pharmaceuticals Corporation is a biopharmaceutical company focused on advancing novel RNAi therapeutics and providing its leading lipid nanoparticle delivery technology to pharmaceutical partners. Tekmira has been working in the field of nucleic acid delivery for over a decade and has broad intellectual property covering LNPs. Further information about Tekmira can be found at www.tekmirapharm.com. Tekmira is based in Vancouver, B.C.
SOURCE: Tekmira Pharmaceuticals
Post Views: 156
Future Clinical Development Plans Outlined for Tekmira’s Oncology Therapeutic, TKM-PLK1
VANCOUVER, Canada I August 12, 2013 I Tekmira Pharmaceuticals Corporation (TKMR) (TKM.TO), a leading developer of RNA interference (RNAi) therapeutics, today announced that it has initiated a Phase I/II clinical trial with TKM-PLK1, its RNAi oncology therapeutic for the treatment of solid tumors.
“We are excited today to outline our broad development plans for TKM-PLK1. Based on the encouraging results from our Phase I clinical trial, we are initiating a Phase I/II clinical trial with TKM-PLK1, which will enroll patients with either advanced Gastrointestinal Neuroendocrine Tumors (GI-NET) or Adrenocortical Carcinoma (ACC). By focusing on these indications, where we observed drug activity in the Phase I trial, we aim to collect additional data on the efficacy of TKM-PLK1 to guide our future development and regulatory strategy for this promising agent. We expect to have results from this completed trial by mid-2014, and if supported by the data, commence a pivotal trial in GI-NET in 2014. In addition, we anticipate initiating a separate Phase I/II clinical trial with TKM-PLK1, which will enroll patients with Hepatocellular Carcinoma (HCC) in the first half of 2014,” said Dr. Mark J. Murray, Tekmira’s President and CEO.
The GI-NET and ACC Phase I/II clinical trial will be a multi-center, single arm, open label study designed to measure efficacy using RECIST and tumor biomarkers for GI-NET patients, as well as to evaluate the safety, tolerability and pharmacokinetics of TKM-PLK1. TKM-PLK1 will be administered weekly with each four-week cycle consisting of three once-weekly doses followed by a rest week. It is expected that approximately 20 patients with advanced GI-NET or ACC tumors will be enrolled in this trial, with a minimum of 10 GI-NET patients to be enrolled.
Tekmira will also initiate another Phase I/II clinical trial with TKM-PLK1, enrolling patients with Hepatocellular Carcinoma (HCC) in the first half of 2014. This clinical trial will be a multi-center, open label, non-randomized, dose escalation study designed to evaluate the safety, tolerability and pharmacokinetics of TKM-PLK1 as well as determine the maximum tolerated dose in HCC patients and measure the anti-tumor activity of TKM-PLK1 in HCC patients.
“Tekmira has completed its Phase I expansion cohort study examining safety of the established maximum tolerated dose (MTD) for TKM-PLK1 in advanced solid tumors. In the expansion cohort, TKM-PLK1 has been administered to a total of 12 patients. To date, four patients are evaluable for efficacy, having received two cycles of TKM-PLK1. Of those four patients, one patient with ACC achieved stable disease. No GI-NET patients were enrolled in this expansion cohort. Thus, we are looking forward to focusing on patients with GI-NET or ACC tumors in this newly initiated trial,” added Dr. Murray.
About TKM-PLK1
Tekmira’s lead oncology product candidate, TKM-PLK1, targets polo-like kinase 1 (PLK1), a protein involved in tumor cell proliferation and a validated oncology target. Inhibition of PLK1 expression prevents the tumor cell from completing cell division, resulting in cell cycle arrest and death of the cancer cell. PLK1 has been a target of interest for years, and evidence that patients with elevated levels of PLK1 in their tumors exhibit poorer prognosis and survival rates has been documented in the medical literature. By using an RNAi approach and exploiting its naturally occurring mechanism of action, Tekmira can potentially overcome the limitations of other approaches and effectively silence PLK1.
In April 2013, results from the dose escalation portion of a Phase I clinical trial were presented at the 2013 American Association for Cancer Research (AACR) Annual Meeting. TKM-PLK1, which employs a unique lipid nanoparticle (LNP) formulation for oncology applications, was administered to 24 patients at doses ranging from 0.15 mg/kg to 0.90 mg/kg; with a total of 152 doses administered and a mean number of 6.2 doses per patient (range of 1-31 doses). Based on these data, the maximum tolerated dose is estimated to be 0.75 mg/kg. Forty-four percent (4 out of 9) of patients evaluable for response, treated at a dose equal to or greater than 0.6 mg/kg, showed clinical benefit. In particular, one patient with progressive, metastatic appendiceal carcinoid (neuroendocrine) cancer had a durable partial tumor response based on RECIST criteria, continuing for more than 10 months. Three other patients achieved stable disease, including one patient with metastatic appendiceal carcinoid (neuroendocrine) cancer, another patient with metastatic colorectal cancer, and a third patient with metastatic adrenocortical carcinoma.
About Gastrointestinal Neuroendocrine Tumors (GI-NET)
Neuroendocrine tumors (NETs) refers to a group of unusual and complex cancers that affect neuroendocrine cells, with those arising in the gastrointestinal tract referred to as GI-NET. It is estimated that there has been a four-fold increase in the incidence of NETs between 1973 and 2004. Approximately 55,000 people are living with GI-NET in the United States. There is a poor prognosis for advanced metastatic NETs, with 25% of patients surviving less than one year. The treatment of patients with gastrointestinal neuroendocrine tumors remains a challenge, and currently there are no approved drugs or treatments indicated specifically for GI-NET.
About Adrenocortical Carcinoma (ACC)
Adrenocortical Carcinoma (ACC) is a rare cancer that forms in the outer layer of tissue of the adrenal gland (a small organ on top of each kidney that makes steroid hormones, adrenaline, and noradrenaline to control heart rate, blood pressure, and other body functions). Even with appropriated diagnosis and treatment, most patients will develop recurrence and succumb to ACC because of the underlying tumor biology, the difficulty of achieving a complete resection, and the lack of effective systemic therapies.
About Hepatocellular Carcinoma (HCC)
Primary liver cancer, or hepatocellular carcinoma (HCC), is one of the most common cancers worldwide, with more than 630,000 people diagnosed each year. HCC represents a major unmet medical need and is associated with one of the poorest survival rates in oncology, in part because only 10-20% of hepatocellular carcinomas can be removed completely using surgery.
About RNAi and Tekmira’s LNP
RNAi therapeutics have the potential to treat a broad number of human diseases by “silencing” disease causing genes. The discoverers of RNAi, a gene silencing mechanism used by all cells, were awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi therapeutics, such as “siRNAs,” require delivery technology to be effective systemically. Tekmira believes its LNP technology represents the most widely adopted delivery technology for the systemic delivery of RNAi therapeutics. Tekmira’s LNP platform is being utilized in multiple clinical trials by both Tekmira and its partners. Tekmira’s LNP technology (formerly referred to as stable nucleic acid-lipid particles or SNALP) encapsulates siRNAs with high efficiency in uniform lipid nanoparticles that are effective in delivering RNAi therapeutics to disease sites in numerous preclinical models. Tekmira’s LNP formulations are manufactured by a proprietary method which is robust, scalable and highly reproducible, and LNP-based products have been reviewed by multiple FDA divisions for use in clinical trials. LNP formulations comprise several lipid components that can be adjusted to suit the specific application.
About Tekmira
Tekmira Pharmaceuticals Corporation is a biopharmaceutical company focused on advancing novel RNAi therapeutics and providing its leading lipid nanoparticle delivery technology to pharmaceutical partners. Tekmira has been working in the field of nucleic acid delivery for over a decade and has broad intellectual property covering LNPs. Further information about Tekmira can be found at www.tekmirapharm.com. Tekmira is based in Vancouver, B.C.
SOURCE: Tekmira Pharmaceuticals
Post Views: 156
