Eli Lilly and Company is planning to expand its lab space at the Alexandria Center for Life Science in New York City to include a translational immuno-oncology hub that will serve as a "portal" for collaborating with researchers from nearby academic medical centers and biopharmaceutical companies.
Jan Lundberg, PhD
The next generation of anticancer immunotherapy will feature combination regimens, making it imperative to move promising treatments into clinical studies at earlier stages, according to research leaders at Eli Lilly and Company.
That is a central reason that Lilly is planning to expand its lab space at the Alexandria Center for Life Science in New York City to include a translational immuno-oncology hub that will serve as a “portal” for collaborating with researchers from nearby academic medical centers and biopharmaceutical companies, Lilly executives said.
The company plans to add 30,000 square feet of lab space and approximately 50 new jobs to its research facilities at the East River Science Park, where about 130 people are currently employed in research and development. The new lab is scheduled for completion in 2016. Lilly officials say the lab expansion is part of a more aggressive approach to immunotherapy development for the Indianapolis-based company, which lags behind its competitors in bringing checkpoint blockade agents to market. The company’s strategy involves numerous partnerships, including cooperating with industry rivals on combination drug trials.
“We are prepared to push the boundaries to accelerate drug discovery,” Jan Lundberg, PhD, executive vice president of science and technology and president of Lilly Research Laboratories, said in a press release announcing the expansion.
In an interview, Lundberg said the focus in immunotherapy would be to design “smart trials” with therapies tailored to patient populations most likely to benefit from them.
Michael Kalos, PhD, chief scientific officer of cancer immunobiology for Lilly, said a key focus of the company’s immunotherapy research efforts would be investigating molecules that could be safely and effectively combined starting in early-phase clinical trial stages.
“So far the field has basically been doing combinations by throwing spaghetti on a wall more or less—‘we have these molecules let’s test them with everything else and see if something works,’” said Kalos. “Lilly’s strategy is really to obtain a deep mechanistic understanding in our models about why molecules might be working or might not be working so that we can appropriately develop and tailor our strategies.”
Kalos said combinations will be important in creating the next generation of immunotherapy. He noted that approximately 70% to 80% of patients typically do not respond to antibodies targeting the PD-1 or CTLA-4 immune checkpoints.
“The field is recognizing that as great as this is and as foundational as it is, there has to be a next generation in this space, and that space is going to be based on combinations and it’s going to be based on understanding more completely why patients are responding or not responding,” said Kalos.
Kalos, who joined Lilly two years ago, is an expert in T-cell immunotherapy who helped lead groundbreaking research at the University of Pennsylvania into the chimeric antigen receptor T-cell therapies that are generating much excitement in hematologic malignancies.
Michael Kalos, PhD
He said an evolving understanding of the immune system would help Lilly researchers evaluate established agents and molecules already in its pipeline in the context of their impact upon anticancer immunity. “The ones we’ve developed don’t target the T cell, they target the microenvironment, which we now know is a critical component for the success of immunotherapy,” said Kalos.
Lilly’s immunotherapy projects include the small molecule galunisertib (LY2157299), which selectively blocks signaling in the transforming growth factor β (TGFβ) pathway.
The agent is being evaluated with and without the multikinase inhibitor sorafenib in phase II studies in hepatocellular carcinoma (HCC).1,2 Additionally, a phase Ib/II study will test the agent in combination with the PD-1 inhibitor nivolumab (Opdivo) in advanced cancers including solid tumors, HCC, non—small cell lung cancer (NSCLC), and glioblastoma.3
Another Lilly agent that is being explored in immunotherapeutic combinations is ramucirumab (Cyramza), which has been approved in metastatic colorectal cancer, NSCLC, and gastric or gastroesophageal junction adenocarcinoma since gaining its initial FDA indication in April 2014.
Ramucirumab is a VEGF receptor 2 antiangiogenic inhibitor that affects the tumor microenvironment, Kalos said. In May, Lilly announced plans to study ramucirumab in combination with the PD-L1 inhibitor durvalumab (MEDI4736) in advanced solid tumors.
Lilly also has early-stage programs investigating antibodies that inhibit CSF1R and CXCR4 receptors in combination with checkpoint inhibitors, and is working on novel and existing checkpoint modulating agents, Kalos said.
Lundberg said that developing new combinations is more complex than evaluating single agents because of the need to optimize the doses for each component of a regimen as well as to identify the optimal tumor type and stage of therapy.
In immunotherapy combinations, Lundberg said, “It’s still early days.”