SAN FRANCISCO, CA, USA I October 7, 2015 I Nektar Therapeutics (NASDAQ: NKTR) today announced that it has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for NKTR-214, its lead immuno-oncology candidate. NKTR-214 is a CD122-biased immune-stimulatory cytokine that is designed to stimulate the patient’s own immune system to destroy cancer cells. The company plans to initiate a Phase 1/2 clinical study by the end of 2015. The study will evaluate the safety, tolerability and efficacy of NKTR-214 in patients with solid tumor malignancies and will include expansion cohorts that will evaluate NKTR-214 both as a single-agent and in combination with a checkpoint inhibitor.
“As a new cytokine with biased receptor activity and an antibody-like dosing schedule, NKTR-214 could emerge as a differentiated immuno-oncology therapy that specifically stimulates T-cell growth to fight cancer,” said Stephen Doberstein, PhD, Senior Vice President and Chief Scientific Officer of Nektar. “In preclinical studies with NKTR-214, we not only observed single-agent efficacy in multiple tumor models, but when administered in combination with a checkpoint inhibitor, we see a dramatic immune-educating vaccine-like effect with NKTR-214. We are excited to start our first-in-human study and we expect to have initial data from the dose-escalation phase of the trial by the second half of 2016.”
The Phase 1/2 clinical program will be conducted at multiple clinical sites including MD Anderson Cancer Center and Yale Cancer Center. In addition to the Phase 1/2 clinical program, Nektar and MD Anderson will conduct translational research to identify predictive biomarkers that can be used in the future development of NKTR-214.
About NKTR-214
NKTR-214 is a CD122-biased immune-stimulatory cytokine that is designed to preferentially stimulate the expansion and maintenance of CD8-positive effector T cells, which are tumor-killing cells found naturally in the body. CD122, which is also known as the Interleukin-2 (IL-2) receptor beta subunit, is a key signaling receptor that is known to increase the proliferation of CD8-positive effector T cells.1 These tumor-killing cells comprise a key component of the tumor infiltrating lymphocytes that provide cell-mediated anti-tumor effects.1 By biasing activation to the CD122 receptor, NKTR-214 enhances the generation of CD8-positive T cells in the tumor.
In preclinical studies, a single dose of NKTR-214 resulted in an approximate 400-fold AUC exposure within the tumor compared with an equivalent dose of aldesleukin, an existing IL-2 therapy. This increase potentially enables, for the first time, an antibody-like dosing regimen for a cytokine.2
At the Inaugural CRI-CIMT-EATI-AACR Immunotherapy Conference in New York in September 2015, Nektar presented data demonstrating that NKTR-214 induces durable and specific anti-tumor immunity as a single agent and when combined with checkpoint inhibitors in preclinical models. As a single agent, NKTR-214 demonstrated efficacy in multiple preclinical models. In combination with either anti-CTLA4 or anti-PD-1 checkpoint inhibitor therapies, NKTR-214 produced durable anti-tumor immunotherapeutic effects, which persisted long after the termination of dosing. In a preclinical tumor re-challenge study, sequential dosing of anti-CTLA-4 followed by NKTR-214 resulted in durable and complete responses. At 142 days following the final dose, with no additional treatment, the complete responders demonstrated sustained resistance to multiple tumor re-challenges. In highly-resistant established melanoma tumor models, treatment with NKTR-214 resulted in a controlled, sustained and biased T-cell activating signal and a mean ratio of CD8-positive T cells to CD4-positive regulatory T-cells (which can suppress tumor killing) of 450:1 in the tumor infiltrating lymphocytes.
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. NKTR-171, a wholly-owned new sodium channel blocker being developed as an oral therapy for the treatment of peripheral neuropathic pain, is in Phase 1 clinical development. In hemophilia, ADYNOVATE™ [Antihemophilic Factor (Recombinant)], a longer-acting PEGylated Factor VIII therapeutic has been filed for approval in the U.S. by partner Baxalta Inc. 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 nine approved products in the U.S. or Europe through partnerships with leading biopharmaceutical companies, including AstraZeneca’s MOVANTIK™, 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: 34
SAN FRANCISCO, CA, USA I October 7, 2015 I Nektar Therapeutics (NASDAQ: NKTR) today announced that it has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for NKTR-214, its lead immuno-oncology candidate. NKTR-214 is a CD122-biased immune-stimulatory cytokine that is designed to stimulate the patient’s own immune system to destroy cancer cells. The company plans to initiate a Phase 1/2 clinical study by the end of 2015. The study will evaluate the safety, tolerability and efficacy of NKTR-214 in patients with solid tumor malignancies and will include expansion cohorts that will evaluate NKTR-214 both as a single-agent and in combination with a checkpoint inhibitor.
“As a new cytokine with biased receptor activity and an antibody-like dosing schedule, NKTR-214 could emerge as a differentiated immuno-oncology therapy that specifically stimulates T-cell growth to fight cancer,” said Stephen Doberstein, PhD, Senior Vice President and Chief Scientific Officer of Nektar. “In preclinical studies with NKTR-214, we not only observed single-agent efficacy in multiple tumor models, but when administered in combination with a checkpoint inhibitor, we see a dramatic immune-educating vaccine-like effect with NKTR-214. We are excited to start our first-in-human study and we expect to have initial data from the dose-escalation phase of the trial by the second half of 2016.”
The Phase 1/2 clinical program will be conducted at multiple clinical sites including MD Anderson Cancer Center and Yale Cancer Center. In addition to the Phase 1/2 clinical program, Nektar and MD Anderson will conduct translational research to identify predictive biomarkers that can be used in the future development of NKTR-214.
About NKTR-214
NKTR-214 is a CD122-biased immune-stimulatory cytokine that is designed to preferentially stimulate the expansion and maintenance of CD8-positive effector T cells, which are tumor-killing cells found naturally in the body. CD122, which is also known as the Interleukin-2 (IL-2) receptor beta subunit, is a key signaling receptor that is known to increase the proliferation of CD8-positive effector T cells.1 These tumor-killing cells comprise a key component of the tumor infiltrating lymphocytes that provide cell-mediated anti-tumor effects.1 By biasing activation to the CD122 receptor, NKTR-214 enhances the generation of CD8-positive T cells in the tumor.
In preclinical studies, a single dose of NKTR-214 resulted in an approximate 400-fold AUC exposure within the tumor compared with an equivalent dose of aldesleukin, an existing IL-2 therapy. This increase potentially enables, for the first time, an antibody-like dosing regimen for a cytokine.2
At the Inaugural CRI-CIMT-EATI-AACR Immunotherapy Conference in New York in September 2015, Nektar presented data demonstrating that NKTR-214 induces durable and specific anti-tumor immunity as a single agent and when combined with checkpoint inhibitors in preclinical models. As a single agent, NKTR-214 demonstrated efficacy in multiple preclinical models. In combination with either anti-CTLA4 or anti-PD-1 checkpoint inhibitor therapies, NKTR-214 produced durable anti-tumor immunotherapeutic effects, which persisted long after the termination of dosing. In a preclinical tumor re-challenge study, sequential dosing of anti-CTLA-4 followed by NKTR-214 resulted in durable and complete responses. At 142 days following the final dose, with no additional treatment, the complete responders demonstrated sustained resistance to multiple tumor re-challenges. In highly-resistant established melanoma tumor models, treatment with NKTR-214 resulted in a controlled, sustained and biased T-cell activating signal and a mean ratio of CD8-positive T cells to CD4-positive regulatory T-cells (which can suppress tumor killing) of 450:1 in the tumor infiltrating lymphocytes.
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. NKTR-171, a wholly-owned new sodium channel blocker being developed as an oral therapy for the treatment of peripheral neuropathic pain, is in Phase 1 clinical development. In hemophilia, ADYNOVATE™ [Antihemophilic Factor (Recombinant)], a longer-acting PEGylated Factor VIII therapeutic has been filed for approval in the U.S. by partner Baxalta Inc. 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 nine approved products in the U.S. or Europe through partnerships with leading biopharmaceutical companies, including AstraZeneca’s MOVANTIK™, 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: 34
