BEIJING – Nanobody startup Sysvax Inc., with its R&D center in Beijing and manufacturing facilities in Zhongshan, is developing a recombinant protein vaccine and a nanobody therapeutic for COVID-19, while trying to extend the half-life of potential COVID-19 treatments with its expertise in this smallest possible antibody format.
To advance its work, it inked a partnership with cell culture specialist Quacell Biotechnology Co. Ltd. (QBD) last week to push forward the vaccine candidate. Sysvax will leverage Quacell’s technology in host cell development and R&D resources. Both sides will also work closely on the pharmaceutical quality while ensuring the supply of core materials.
“We believe developing recombinant protein vaccines is a reliable approach,” Sysvax CEO Li Fusheng told BioWorld. “Our COVID-19 vaccine candidate is our most advanced program currently. We hope to advance it to the clinic faster by working with Quacell.”
He said expects the vaccine candidate to be IND-ready by the end of this year or early 2021.
Last month, Sysvax said animal trials showed that high S1 antibody titers were produced seven days after immunization, and the vaccine candidate was also well-tolerated.
Founded in August 2015 in Beijing to focus on infectious diseases and malignant tumors, Sysvax, like other Chinese biotech companies, swiftly turned its attention to the coronavirus even though it had programs ongoing for other indications such as HIV and tuberculosis.
While the company is better known in the industry as a nanobody specialist, Li said vaccines are another focus, based on its expertise in recombinant protein.
Sysvax has a synthetic virus-like particle (SVLP) nucleic acid delivery technology platform co-developed with the Beijing Institute of Technology, which mimics the structure of natural viruses to produce humoral immunity and cellular immune response. Sysvax said the technology platform can avoid the drawbacks of viral vectors while retaining high delivery efficiency and immunogenicity.
The startup described SVLP as an advanced technology developed from lipid nanoparticles and an ideal nonviral vector platform for delivering DNA and RNA, which can be mRNA, samRNA or even double-stranded RNA. Sysvax noted that could be a better approach than lipid nanoparticle delivery.
Before the COVID-19 vaccine program came along, Sysvax had already begun work in developing vaccines for cervical cancer, HIV and tuberculosis. Li told BioWorld that there are currently seven to eight vaccine candidates in the pipeline.
But to begin with, Sysvax first received industry attention for using nanobodies derived from llama and camels. It is now also developing a COVID-19 nanobody therapeutic besides the recombinant protein vaccine.
This week, the llama-derived antibodies received wide media coverage after a Belgian study reported that those antibodies can help neutralize the virus responsible for COVID-19, igniting public interest in the technology.
Talking about the potential of nanobodies, Li said: “One of its advantages is that it can be developed into bispecific or multifunctional antibodies.”
Another approach is to use nanobodies to extend the half-life of polypeptides, Li explained. “For the coronavirus, ACE2 has a short half-life. If fused to nanobodies, we can extend its half-life by one to two weeks. This means COVID-19 patients will only need one treatment.”
Sysvax has a bispecific platform called Nanobody Bispecific T-cell Engager (nanoBiTE), which combines two nanobodies with each arm recognizing T-cell and tumor cell antigens, respectively.
It also has other related technology platforms, ranging from nanobody screening and optimization to multifunctional nanobody and large-scale fermentation production.
“We’re a company that can do the entire R&D pipeline in-house,” Li said, adding that Sysvax currently has seven or eight candidates in its nanobody pipeline. One targets the CGRP pathway to treat migraines, while another one is aimed at diabetes.
He also shared that Sysvax is developing neutralizing antibodies using its expertise in nanobody technology – one for COVID-19 and a few more for undisclosed indications. That approach may lower production costs and make mass production easier, he said.
Altogether, Sysvax has around 15 drug candidates under development. Li said more than 10 are in preclinical studies, with two or three soon entering pilot-scale experiments.
Nanobody technology is beginning to grow in China’s biotech scene. Startups such as Sichuan NB Biolab Co. Ltd., Shenzhen Innova Nanobodi Co. Ltd. and Persongen Anke Cellular Therapeutics Co. Ltd. are also joining the course.
Seeing the potential in that technology, investors contributed ¥50 million (US$7 million) in Sysvax’s pre-A financing round on Feb. 27, 2020. Before founding the company, Li had served at the Fred Hutchinson Cancer Research Center in Seattle, focusing on HIV research, after receiving his biotech training at the Chinese Center For Disease Control And Prevention.