Nektar Therapeutics Chief Science Officer Provides Details on Immuno-Oncology, Pain Pipelines
October 9, 2015
By Alex Keown, BioSpace.com Breaking News Staff
NEW YORK – Stephen Doberstein, chief science officer of New York-based Nektar Therapeutics , touted his company’s experimental IL-2 cancer therapy as a possible tool that could revolutionize the way cancer is treated.
In an exclusive interview with BioSpace prior to Nektar’s Oct. 8 investor and analyst R&D day, Doberstein called NKTR-214, a CD122-biased immune-stimulatory cytokine designed to stimulate the patient's own immune system to destroy cancer cells, an “innovative approach to stimulating the immune system’s response to cancer.”
Doberstein said the idea of immune-oncology has been around for many years, with one drug, Proleukin having been shown to be quite effective, although with several side effects. Doberstein said Nektar is taking a different approach to immuno-oncology than other companies delving into the field of harnessing the body’s immune system to fight cancer infections. Doberstein said Nektar’s approach to immune-oncology is more of a watchmaker’s approach, a fine-tune tweaking of the immune system’s response to cancer. NKTR-214, an early stage cancer drug, is showing the kind of promise that could yield significant success in battling cancer, Doberstein said.
Earlier this month Nektar submitted an investigational new drug application for NKTR-214 a CD122-biased immune-stimulatory cytokine that is designed to stimulate the patient's own immune system to destroy cancer cells. Doberstein said preclinical studies of NKTR-214 shoed both single-agent efficacy in multiple tumor models, as well as an “immune-educating vaccine-like effect” when the drug was administered with checkpoint inhibitors. The company hopes to being Phase I/II clinical trials of NKTR-214 soon.
NKTR-214 is an Interleukin-2 (IL-2) receptor beta subunit designed to preferentially stimulate the expansion and maintenance of CD8-positive effector T cells, which are tumor-killing cells found naturally in the body. The IL-2 receptor is a key signaling receptor is known to increase the proliferation of CD8-positive effector T cells. By activating the receptor, NKTR-214 enhances the generation of CD8-positive T cells in the tumor, according to Nektar’s research.
“Our goal with NKTR-214 is to reeducate the immune system so it says ‘hey, wait a minute. These cells are trying to trick me,’” Doberstein said.
Describing their experimental therapy as a Swiss-Army knife with the potential for multiple applications, Doberstein said NKTR-214 could be used as a combination therapy with other cancer approaches.
Data from preclinical studies are also showing NKTR-214 may not have to be administered in high doses, which means typical side effects associated with cancer treatment might be diminished.
Doberstein said there are many pharmaceutical companies showing promise in the areas of immuno-oncology, including AstraZeneca PLC ’s Durvalumab, a monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. Preclinical data have demonstrated that by combining the enhanced T-cell mediated anti-tumor activity of bavituximab with checkpoint inhibitors like PD-L1 antibodies, the ability of tumor-specific T-cells to continue attacking the tumor is prolonged.
In addition to NKTR-214, the company shared information on its other experimental immuno-oncology agent, NKTR-255. The second therapy is an immune-stimulatory cytokine designed to improve T-cell memory by targeting the IL-15 pathway.
Pain Treatment
During the investor meeting, Nektar unveiled its newest chronic-pain treatment, NKTR-181, a new opiod molecule that has a low abuse liability due to its extended release time. Pain medications, such as Oxycodone, are often one of the most abused drugs due to its quick effect on the brain. Ivan Gergel, Nektar’s chief medical officer, said Oxycodone reaches its peak effect in about 11 minutes, making it a prime drug for abuse.
Doberstein said the trick in developing a new treatment for chronic pain was to slow the rate of the drug’s entry into the brain, which would lower the potential for abuse.
“This is something we’ve shown in preclinical trials,” Doberstein said.
During the investor meeting, Gergel said NKTR-181 has a peak release time of about three hours, something he said they were hoping to see. Jack Henningfield, Pinney Associate’s vice president of research and health policy, said the drug will appear to satisfy new federal pain medication guidelines and could possibly achieve a more favorable scheduling level, possibly a Schedule 3 drug.
NKTR-181 will help expand Nektar’s pain medication offerings. Nektar’s pain drug Movantik, created alongside AstraZeneca, an oral treatment for opioid-induced constipation in adults with chronic non-cancer pain, was approved by the FDA in 2014. Opiods, commonly used to treat pain, have a side effect that can make having a bowel movement difficult. The medication is projected to generate revenue of nearly $2 billion by 2017.