The first bispecific antibody to win regulatory approval, Removab (catumaxomab), was voluntarily withdrawn due to commercial reasons. Now Chinese biotech Lintonpharm Co. Ltd., of Guangzhou, said it plans to move catumaxomab to a global phase III trial following an IND approval from China’s NMPA, investigating the trifunctional bispecific antibody in patients with peritoneal carcinomatosis, a form of advanced gastric cancer.
Focusing on T-cell engaging bispecific antibodies, Lintonpharm was established in 2017 by Xiao Shen and Horst Lindhofer, CEOs of Chinese CDMO Canton Biologics Co. Ltd. and Germany-based Lindis Biotech GmbH, respectively. Lindhofer was also the co-founder of Trion Pharma GmbH, the originator and developer of catumaxomab.
This time, the Chinese startup is initiating a two-stage, multicenter, open-label, randomized, controlled registrational clinical trial to evaluate the safety and efficacy of an intraperitoneal infusion of catumaxomab into the abdominal cavity in patients with peritoneal carcinomatosis.
Robert Li, CEO of Lintonpharm, told BioWorld that the second stage is expected to start in the third quarter of 2021.
The study expects to enroll 297 subjects, with 15 subjects in the first stage at most and 282 evaluable subjects in the second stage. In the first stage, the pharmacokinetic characteristics and preliminary safety of catumaxomab will be explored in Asian patients with gastric cancer, while in the second stage, the subjects will be randomized and given either a catumaxomab infusion or a treatment of the investigator’s choice at a ratio of 2-to-1.
The company also received green lights for trials of the bispecific candidate in Taiwan and Korea. “Patient enrollment in both regions is expected in the third quarter of 2020,” Li said.
Lintonpharm also has plans for U.S. trials of catumaxomab for peritoneal carcinomatosis in late 2021 or early 2022.
Footprint in the EU
Catumaxomab previously gained approval in the EU under the trade name Removab in 2009. Originated from German firms Trion Pharma and Fresenius Biotech GmbH, catumaxomab is known to be the first T-cell engaging bispecific antibody approved in Europe to treat malignant ascites in adults with EpCAM-positive carcinomas where standard therapy is not available or no longer feasible.
But the drug has not been marketed in the EU since 2014, and its market authorization was subsequently voluntarily withdrawn in the region in 2017, when manufacturer Neovii Biotech GmbH became insolvent.
Still, promising data from catumaxomab has encouraged Lintonpharm to put it back on the market. In re-initiating clinical development, Li said the antibody “may have benefit in a broad range of cancers” and has “a robust foundation of clinical data” that support its therapeutic potential in advanced gastric cancer.
“Catumaxomab has demonstrated therapeutic potential in gastric cancer patients with malignant ascites in a previous pivotal trial for malignant ascites,” Li told BioWorld. “The overall survival of the 66 gastric cancer patients in the malignant ascites trial was 71 days versus 44 days in the control group (‘p’ value of 0.0313, HR of 0.469).”
Data supporting its 2009 approval included results from a phase II/III trial in advanced cancer patients with malignant ascites, showing catumaxomab attained the primary endpoint and several secondary endpoints.
To be continued in China
Lintonpharm said catumaxomab originated from the Triomab platform. The drug binds to a transmembrane glycoprotein on the tumor cell EpCAM and CD3 on T cells, and also recruits immune accessory cells through FcγR binding. It kills tumor cells by engaging T-cell and accessory cell-mediated cytotoxicity and has the potential to induce long-term vaccinal effects against tumor cells due to its FcγR binding and activation profile.
Lindhofer is the developer of the Triomab platform, which is a chimeric bispecific antibody platform designed to augment the normal immune recruitment functions associated with traditional antibody molecules. He founded Trion Pharma in 1998 to commercialize that asymmetric bispecific antibody format with classical IgG structure.
Almost two decades later, he co-founded Lintonpharm in China and now serves as chief scientific officer to continue the clinical development of catumaxomab, now the company’s lead program. The firm also has several treatments in development for blood cancer and solid tumors.
The Chinese biotech and Lindhofer are also developing a next-generation bispecific antibody platform called Fleximab to provide better CMC developability and less immunogenicity.
“Both Triomab and Fleximab carry fine-tuned Fc which could lead to potential vaccinal effects for long-term antitumor immunity,” Li said. “In addition, CD3 Fab has unique binding features that may lead to an improved safety profile.”
Positioning itself as a research-oriented company, Lintonpharm’s goal is to use both the Triomab and Fleximab platforms to develop innovative T-cell engaging bispecific antibodies to make malignant cancers manageable and possibly curable.
A series A financing round in 2018 raised about $15 million, and the company is looking to complete a series B round by the end of the third quarter of 2020, Li told BioWorld.
Li joined the company as a co-founder and CEO in early 2020 to restructure the pipeline and overall development strategy.
This year, the company is also preparing IND filings for two other molecules, but Li said “that's not information we're ready to disclose at this time.”