NORTH CHICAGO, Ill. & LA JOLLA, Calif.—The whole idea behind chimeric antigen receptor T cell (CAR-T) therapies is to tap into the potential of the patient’s own immune system to fight cancer. But as much as CAR-T has been in the news lately, there is much work still to do. To that end, global biopharmaceutical company AbbVie has teamed up with Calibr (California Institute for Biomedical Research), a nonprofit drug discovery division of Scripps Research, to develop the next generation of T cell therapies.
Although oncology isn’t the only potential application for CAR-T, the effort is aimed primarily at cancer—and solid tumors in particular. And for AbbVie, one of the advantages in this pairing is that it will broaden the company’s oncology research to access advanced precision medicine technology and expand its development of therapeutics for patients with cancer.
One of the prompting factors in forming this partnership is the fact that while CAR-T has some promise with regard to hematological cancers, current CAR-T therapies in development for solid tumors have demonstrated limitations, the reason being that the rapid activation and expansion of CAR-T cells can lead to serious adverse events.
That’s where Calibr’s novel cell therapy program comes in. The program, led by Dr. Travis Young, the director of protein sciences at Calibr, is designed to enhance safety, versatility and efficacy through a proprietary modular “switchable” CAR-T cell that uses antibody-based switch molecules to control the activation and antigen specificity of CAR-T cells, according to the research partners. The partners add that Calibr’s proprietary technology may enable the development of universal CAR-T-based treatments across several types of hematological and solid tumor indications.
Under the terms of the license agreement, AbbVie will pay Calibr an upfront fee and gain exclusive access to Calibr’s switchable CAR-T platform for a period of as long as four years. The two organizations will work together to develop T cell therapies directed to solid tumor targets identified by AbbVie, which also has the option to develop additional cell therapies toward AbbVie-nominated targets and license existing Calibr cell therapy programs under development for hematological and solid cancers, including Calibr’s lead program. Calibr plans to enter this lead candidate into clinical studies for lymphoma in 2019. In addition, the agreement provides AbbVie with an option to acquire an exclusive license to Calibr’s switchable CAR-T platform and programs within the first four years of the collaboration. The companies will share responsibility for preclinical development, with AbbVie responsible for clinical development and commercialization, and Calibr eligible to receive success-based milestone payments and royalties.
“Calibr has assembled a premier scientific team and developed an innovative cell therapy technology that can take us to the next frontier of cancer treatment,” said Dr. Mohit Trikha, AbbVie vice president and head of the Oncology Early Development program at the company. “The combination of AbbVie’s oncology discovery and early development expertise and Calibr’s novel switchable CAR-T therapy platform aims to advance the current standard of care, with the potential rapidly advancing new treatment options for patients.”
A benefit for Calibr in this team-up is that having a “strong partner” like AbbVie can help Calibr expand the impact of the CAR-T cell field to a broader range of cancers, noted Dr. Peter Schultz, CEO of Calibr and Scripps Research.
In other recent cancer news from AbbVie, the U.S. Food and Drug Administration (FDA) recently accepted for priority review a supplemental New Drug Application (sNDA) for Imbruvica (ibrutinib) in combination with Rituxan (rituximab) as a new treatment option for Waldenström’s macroglobulinemia (WM). If approved, the sNDA would expand the prescribing information of Imbruvica in WM beyond its current approved use—as a single agent for all lines of therapy—to include combination use with rituximab. As a single-agent therapy, Imbruvica is the first and only FDA-approved treatment available for patients with WM. Imbruvica is a first-in-class Bruton’s tyrosine kinase inhibitor jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech Inc.
“We are excited about the data from the Phase 3 iNNOVATE study, which indicate that Imbruvica plus rituximab was able to improve progression-free survival versus rituximab alone, across all lines of therapy and Waldenström’s macroglobulinemia patient subgroups that were studied,” remarked Dr. Thorsten Graef, head of clinical development at Pharmacyclics. “These promising findings build on our commitment to exploring the full potential of Imbruvica alone and in combination with other treatments. If approved, this chemotherapy-free combination will provide another treatment opportunity for patients living with this rare disease, which continues to have very limited treatment options.”
The sNDA is supported by data from the Phase 3 iNNOVATE (PCYC-1127) trial assessing Imbruvica in combination with rituximab versus rituximab alone in patients with previously untreated and relapsed/refractory WM. These data were recently presented at the American Society of Clinical Oncology 2018 Annual Meeting and simultaneously published in The New England Journal of Medicine.
Waldenström’s macroglobulinemia is a rare and incurable form of non-Hodgkin’s lymphoma. There are about 2,800 new cases of WM in the United States each year. In January 2015, Imbruvica received FDA approval for all lines of treatment in WM and as the first and only FDA-approved therapy specifically indicated for this disease.