HONG KONG – Carsgen Therapeutics Ltd. and Shanghai Cancer Institute entered a five-year research and development agreement for Carsgen's chimeric antigen receptors T-cell (CAR-T) cancer immunotherapeutic candidates. The partners will work together to discover and develop CAR-T candidates as well as next-generation CAR-T drug candidates.

"We have long been a partner with Shanghai Cancer Institute, the staff has over a decade's experience in immunotherapy," Zonghai Li, president and CEO of Carsgen, told BioWorld Today. "They have China's first key lab for oncogene and related gene, and the affiliation it has with Renji Hospital is another benefit."

"It's a win-win situation for all of us," said Li.

Under terms of the agreement, Carsgen will retain the commercial rights of all the intellectual assets generated from the collaboration. Financial details were not disclosed.

Founded in 1958, the Shanghai Cancer Institute has been an independent research institution specializing in cancer. It has major research laboratories such as State Key Laboratory of Oncogene and Related Genes, Epidemiology Laboratory, Molecular and Immunological Diagnosis and others.

In May 2015, Carsgen inked an agreement with Shanghai Jiaotong University, affiliated with Renji Hospital, to develop Carsgen's glypican-3 (GPC3) CAR-T candidate for the treatment of relapsed or refractory hepatocellular carcinoma (HCC), or advanced liver cancer. GPC3 is expressed in a variety of tumors, with a high frequency in HCC.

Liver resection surgery is by far the most effective treatment for HCC, but tumor recurrence is very high. Most HCC patients are diagnosed at a late stage, so a lot of the existing curative therapies wouldn't work by the time they learn about their situation.

Last year, Carsgen received an investment from major Chinese life science investor BVCF, and has been the first Chinese immunotherapy company to start a clinical study in human liver cancer. Most of the proceeds were used on the clinical trial for Carsgen's GPC3-CAR-T candidate. (See BioWorld Today, Dec. 2, 2014.)

Carsgen and Renji Hospital started enrolling patients in March for a phase I study of the GPC3-CAR-T therapy to evaluate its safety and early stage efficacy. The ongoing trial has enrolled six patients with relapsed or refractory HCC and treated them with escalating doses of GPC3-CAR-T infusions.

No adverse events have been observed in the trial so far. Two of the six patients demonstrated more than 90 percent decline in levels of alpha-fetoprotein (AFP), a liver biomarker indicating the level of activity of cancer cells. Another patient's AFP levels were back to normal range after two months of treatment.

"The preliminary clinical data accumulated from the first six patients is very encouraging," said Li. "It helps us to identify additional parameters including on-target off-tumor toxicity, effective dose regime, and pre-infusion operations."

Carsgen plans to continue the clinical test by enrolling up to 20 patients in the Phase I trial.

"The phase I clinical trial will be finished by the beginning of next year and the phase II clinical trial will start following that within the first half of 2016," said Li. "We are preparing for the second round of financing now and hope to bring the clinical trial to the US soon.

"Immunotherapy is much like stem cell therapy, there was no clear regulation in China and the local market was messy," said Li. "Now that the CFDA has come up with regulations for stem cell research, we hope the same will happen with immunotherapy soon, too."

In addition to its GPC3-CAR-T program, Carsgen has a broad range of CAR-T candidates for lung, brain and stomach cancers. Carsgen and Renji Hospital have begun to enroll up to 10 patients in a phase I study of an anti-EGFR CAR-T therapy for the treatment of brain cancer. The company also has gastric cancer candidate CSG-002, pancreatic cancer candidate CSG-004, ovarian cancer candidate CSG-005, and neuroblastoma candidate CSG-007 in the pipeline at preclinical stage.

"Immunotherapy products are not regulated yet. We can't register our products, so we're doing the drug development as a research project of the hospital," he added. "Immunotherapy for cancer is a major trend in the future, so we're confident that there will be regulations soon and the market has huge potential."