SAN FRANCISCO, CA, USA I February 1, 2016 I Nektar Therapeutics (Nasdaq: NKTR) today announced the publication in Clinical Cancer Research of pre-clinical findings for NKTR-214. The paper, titled “NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models,” (Charych et al., Clin Cancer Res, doi:10.1158/1078-0432.CCR-15-1631) documents a broad set of pre-clinical data supporting the clinical advancement of NKTR-214. Among the findings reported, treatment with NKTR-214 led to durable and specific anti-tumor immunity in multiple syngeneic mouse models both as a single agent and as combination therapy with checkpoint inhibitors. In addition, treatment with single-agent NKTR-214 in tumor-bearing mice resulted in a controlled, sustained, and biased T-cell activation leading to a 450:1 mean ratio of CD8-positive effector T cells to T-regulatory cells in the tumor microenvironment, while maintaining more balanced ratios in non-tumor tissues and circulation.
“NKTR-214 allows us to capture and harness the power of the IL-2 biological pathway, which is known to promote T cell growth, to stimulate the body’s own immune system to target and fight cancer. The design of NKTR-214 gives it a combination of biophysical, biochemical, and pharmacological properties that translate into a desirable anti-tumor immune profile,” said Stephen Doberstein, Ph.D., Senior Vice President and Chief Scientific Officer of Nektar Therapeutics.
The newly published data documented in the paper also support the favorable safety profile of NKTR-214. The compound was well-tolerated in rodents and in non-human primates (NHPs). Importantly, these pre-clinical safety studies showed that NKTR-214 did not lead to hypotension or vascular leak syndrome at predicted clinical therapeutic doses.
As documented in the new publication, in a pre-clinical tumor re-challenge study in an EMT6 mouse breast cancer model, dosing of NKTR-214 in combination with anti-CTLA-4 antibody resulted in durable and complete responses lasting up to 170 days (5.5 months). When tumor-free animals were re-challenged with the same tumors with no additional treatment, the complete responders demonstrated sustained vaccine-like resistance. These results suggest that NKTR-214 provides a complementary mechanism of immune activation when used concurrently with approved antibody therapies.
“We are pleased that the unique mechanism, efficacy and safety of NKTR-214 are now described and published in a prestigious peer-reviewed journal that is widely read by oncologists, scientists and physician-scientists,” said Dr. Doberstein. “We are continuing to advance NKTR-214 in an ongoing Phase 1/2 clinical trial in cancer patients and we expect to have preliminary top-line results from the first stage of this study in the second half of 2016.”
About the NKTR-214 Phase 1/2 Clinical Study
NKTR-214 is currently being evaluated in a Phase 1/2 clinical study in patients with advanced solid tumors, including melanoma, renal cell carcinoma and non-small cell lung cancer. The ongoing study is being conducted at MD Anderson Cancer Center and Yale Cancer Center and is comprised of two stages. The first stage is an open-label, multi-dose, dose-escalation study evaluating single-agent NKTR-214 treatment in approximately 20 patients with solid tumors. The primary objective of the first stage of the study is to evaluate the safety and efficacy of NKTR-214, and to define the recommended Phase 2 dose. In addition, the study will assess preliminary anti-tumor activity, including objective response rate (ORR). The immunologic effect of NKTR-214 on tumor-infiltrating lymphocytes (TILs) and other immune cells in both blood and tumor tissue will also be assessed. Following the dose-escalation stage of the study, dose expansion cohorts are planned to evaluate NKTR-214 in specific tumor types, including melanoma, renal cell carcinoma and non-small cell lung cancer.
For more information on the ongoing NKTR-214 Study, please visit the “Clinical Trials” section of www.mdanderson.org using identifier 2015-0573 or visit https://medicine.yale.edu/cancer/research/trials/active/858.trial.
About NKTR-214
NKTR-214 is a CD122-biased immune-stimulatory cytokine, which is designed to stimulate the patient’s own immune system to kill tumor cells. By biasing activation to the CD122 receptor, NKTR-214 enhances CD8+ effector T cells (tumor-killing cells) in the tumor. In pre-clinical studies, a single dose of NKTR-214 resulted in a 400-fold AUC exposure within the tumor compared with an equivalent dose of the existing IL-2 therapy, enabling, for the first time, an antibody-like dosing regimen for a cytokine.
About Nektar
Nektar Therapeutics has a robust R&D pipeline in pain, oncology, hemophilia and other therapeutic areas. In the area of pain, Nektar has an exclusive worldwide license agreement with AstraZeneca for MOVANTIK™ (naloxegol), the first FDA-approved once-daily oral peripherally-acting mu-opioid receptor antagonist (PAMORA) medication for the treatment of opioid-induced constipation (OIC), in adult patients with chronic, non-cancer pain. The product is also approved in the European Union as MOVENTIG® (naloxegol) and is indicated for adult patients with OIC who have had an inadequate response to laxatives. The AstraZeneca agreement also includes NKTR-119, an earlier stage development program that is a co-formulation of MOVANTIK and an opioid. NKTR-181, a wholly-owned mu-opioid analgesic molecule for chronic pain conditions, is in Phase 3 development. In hemophilia, Nektar has a collaboration agreement with Baxalta for ADYNOVATE™ [Antihemophilic Factor (Recombinant)], a longer-acting PEGylated Factor VIII therapeutic approved in the U.S. in patients over 12 with hemophilia A. In anti-infectives, Amikacin Inhale is in Phase 3 studies conducted by Bayer Healthcare as an adjunctive treatment for intubated and mechanically ventilated patients with Gram-negative pneumonia.
Nektar’s technology has enabled ten approved products in the U.S. or Europe through partnerships with leading biopharmaceutical companies, including AstraZeneca’s MOVANTIK™, Baxalta’s ADYNOVATE™, UCB’s Cimzia® for Crohn’s disease and rheumatoid arthritis, Roche’s PEGASYS® for hepatitis C and Amgen’s Neulasta® for neutropenia.
Nektar is headquartered in San Francisco, California, with additional operations in Huntsville, Alabama and Hyderabad, India. Further information about the company and its drug development programs and capabilities may be found online at http://www.nektar.com.
SOURCE: Nektar Therapeutics
Post Views: 185
SAN FRANCISCO, CA, USA I February 1, 2016 I Nektar Therapeutics (Nasdaq: NKTR) today announced the publication in Clinical Cancer Research of pre-clinical findings for NKTR-214. The paper, titled “NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models,” (Charych et al., Clin Cancer Res, doi:10.1158/1078-0432.CCR-15-1631) documents a broad set of pre-clinical data supporting the clinical advancement of NKTR-214. Among the findings reported, treatment with NKTR-214 led to durable and specific anti-tumor immunity in multiple syngeneic mouse models both as a single agent and as combination therapy with checkpoint inhibitors. In addition, treatment with single-agent NKTR-214 in tumor-bearing mice resulted in a controlled, sustained, and biased T-cell activation leading to a 450:1 mean ratio of CD8-positive effector T cells to T-regulatory cells in the tumor microenvironment, while maintaining more balanced ratios in non-tumor tissues and circulation.
“NKTR-214 allows us to capture and harness the power of the IL-2 biological pathway, which is known to promote T cell growth, to stimulate the body’s own immune system to target and fight cancer. The design of NKTR-214 gives it a combination of biophysical, biochemical, and pharmacological properties that translate into a desirable anti-tumor immune profile,” said Stephen Doberstein, Ph.D., Senior Vice President and Chief Scientific Officer of Nektar Therapeutics.
The newly published data documented in the paper also support the favorable safety profile of NKTR-214. The compound was well-tolerated in rodents and in non-human primates (NHPs). Importantly, these pre-clinical safety studies showed that NKTR-214 did not lead to hypotension or vascular leak syndrome at predicted clinical therapeutic doses.
As documented in the new publication, in a pre-clinical tumor re-challenge study in an EMT6 mouse breast cancer model, dosing of NKTR-214 in combination with anti-CTLA-4 antibody resulted in durable and complete responses lasting up to 170 days (5.5 months). When tumor-free animals were re-challenged with the same tumors with no additional treatment, the complete responders demonstrated sustained vaccine-like resistance. These results suggest that NKTR-214 provides a complementary mechanism of immune activation when used concurrently with approved antibody therapies.
“We are pleased that the unique mechanism, efficacy and safety of NKTR-214 are now described and published in a prestigious peer-reviewed journal that is widely read by oncologists, scientists and physician-scientists,” said Dr. Doberstein. “We are continuing to advance NKTR-214 in an ongoing Phase 1/2 clinical trial in cancer patients and we expect to have preliminary top-line results from the first stage of this study in the second half of 2016.”
About the NKTR-214 Phase 1/2 Clinical Study
NKTR-214 is currently being evaluated in a Phase 1/2 clinical study in patients with advanced solid tumors, including melanoma, renal cell carcinoma and non-small cell lung cancer. The ongoing study is being conducted at MD Anderson Cancer Center and Yale Cancer Center and is comprised of two stages. The first stage is an open-label, multi-dose, dose-escalation study evaluating single-agent NKTR-214 treatment in approximately 20 patients with solid tumors. The primary objective of the first stage of the study is to evaluate the safety and efficacy of NKTR-214, and to define the recommended Phase 2 dose. In addition, the study will assess preliminary anti-tumor activity, including objective response rate (ORR). The immunologic effect of NKTR-214 on tumor-infiltrating lymphocytes (TILs) and other immune cells in both blood and tumor tissue will also be assessed. Following the dose-escalation stage of the study, dose expansion cohorts are planned to evaluate NKTR-214 in specific tumor types, including melanoma, renal cell carcinoma and non-small cell lung cancer.
For more information on the ongoing NKTR-214 Study, please visit the “Clinical Trials” section of www.mdanderson.org using identifier 2015-0573 or visit https://medicine.yale.edu/cancer/research/trials/active/858.trial.
About NKTR-214
NKTR-214 is a CD122-biased immune-stimulatory cytokine, which is designed to stimulate the patient’s own immune system to kill tumor cells. By biasing activation to the CD122 receptor, NKTR-214 enhances CD8+ effector T cells (tumor-killing cells) in the tumor. In pre-clinical studies, a single dose of NKTR-214 resulted in a 400-fold AUC exposure within the tumor compared with an equivalent dose of the existing IL-2 therapy, enabling, for the first time, an antibody-like dosing regimen for a cytokine.
About Nektar
Nektar Therapeutics has a robust R&D pipeline in pain, oncology, hemophilia and other therapeutic areas. In the area of pain, Nektar has an exclusive worldwide license agreement with AstraZeneca for MOVANTIK™ (naloxegol), the first FDA-approved once-daily oral peripherally-acting mu-opioid receptor antagonist (PAMORA) medication for the treatment of opioid-induced constipation (OIC), in adult patients with chronic, non-cancer pain. The product is also approved in the European Union as MOVENTIG® (naloxegol) and is indicated for adult patients with OIC who have had an inadequate response to laxatives. The AstraZeneca agreement also includes NKTR-119, an earlier stage development program that is a co-formulation of MOVANTIK and an opioid. NKTR-181, a wholly-owned mu-opioid analgesic molecule for chronic pain conditions, is in Phase 3 development. In hemophilia, Nektar has a collaboration agreement with Baxalta for ADYNOVATE™ [Antihemophilic Factor (Recombinant)], a longer-acting PEGylated Factor VIII therapeutic approved in the U.S. in patients over 12 with hemophilia A. In anti-infectives, Amikacin Inhale is in Phase 3 studies conducted by Bayer Healthcare as an adjunctive treatment for intubated and mechanically ventilated patients with Gram-negative pneumonia.
Nektar’s technology has enabled ten approved products in the U.S. or Europe through partnerships with leading biopharmaceutical companies, including AstraZeneca’s MOVANTIK™, Baxalta’s ADYNOVATE™, UCB’s Cimzia® for Crohn’s disease and rheumatoid arthritis, Roche’s PEGASYS® for hepatitis C and Amgen’s Neulasta® for neutropenia.
Nektar is headquartered in San Francisco, California, with additional operations in Huntsville, Alabama and Hyderabad, India. Further information about the company and its drug development programs and capabilities may be found online at http://www.nektar.com.
SOURCE: Nektar Therapeutics
Post Views: 185
