BEIJING – One more company is joining the global efforts in developing a vaccine for COVID-19. Beijing-based Yisheng Biopharma Co. Ltd. unveiled YS-SC2-010, which was developed through recombinant protein technology and its proprietary PIKA (polyinosinic-polycytidylic acid-based adjuvant) technology. The company is looking to take it overseas through partnership.

The PIKA adjuvanted recombinant protein vaccine is still in the preclinical stage. Yisheng said it is in talks with regulators to move YS-SC2-010 to multicenter clinical trials in China, Southeast Asia, the U.S. and Europe once it finishes up animal studies and preclinical preparation.

YS-SC2-010 incorporates a recombinant protein antigen with PIKA adjuvant. In animal models, the vaccine candidate was shown to be highly immunogenic and to induce high levels of neutralizing antibodies.

Yisheng also noted that the recombinant protein antigen was produced in a mammalian cell system with the advantages of safe manufacturing, easy scale-up, high purity, and good antigen specificity and safety.

“We plan to start a phase I/II study to look at the vaccine candidate’s safety and immunogenicity profile and recruit several hundreds of healthy volunteers for the study,” Yisheng CEO David Shao told BioWorld.

Yisheng is known for developing biotherapeutics for cancer and infectious disease with its PIKA immunomodulating technology, which consists of biologic complexes that incorporate an agonist of the TLR3, RIG-I and MDA5 pathways. When delivered with relevant protein-based molecules, PIKA technology can be used to develop antiviral vaccines, antiviral therapeutics and cancer therapeutics.

The PIKA technology, in particular, is crucial in designing a vaccine candidate.

“Without the PIKA adjuvant, the antigen of YS-SC2-010 alone couldn’t generate a sufficient level of neutralizing antibodies in animal studies,” said Yisheng’s founder and chairman, Zhang Yi.

The PIKA adjuvant is a synthetic product acting as an agonist for TLR3. It can activate dendritic cells to produce co-stimulatory molecules and rapidly induce high-level and high-affinity antibodies. Meanwhile, it also induces strong CD4-positive and CD8-positive T-cell-specific immune response.

“[YS-SC2-010] is developed based on the technology platform that we used to develop our therapeutic PIKA rabies vaccine, so we expect it to be both preventive and therapeutic,” Zhang continued.

“As there is an unmet need globally, PIKA adjuvant technology can significantly lower the antigen dose and increase production output to supply the vaccine to more countries and territories,” he added.

Yisheng has been using PIKA adjuvant technology to develop new-generation vaccine candidates, such as PIKA rabies vaccine, PIKA hepatitis B vaccine, PIKA influenza vaccine, PIKA Ebola vaccines and PIKA SARS vaccines. It said the technology has yielded encouraging results in various programs.

In 2016, Yisheng unveiled positive phase I data that showed its PIKA rabies vaccine was well-tolerated and safe while eliciting a multispecific rabies T-cell response. The vaccine required three injections in seven days to produce 100% seroconversion on day 14, and 75% of subjects achieved seroconversion on day seven. In the same year, the FDA granted it orphan drug designation.

As for the PIKA SARS vaccine, Yisheng said it can significantly increase the levels of IgG and IgA in serum and mucosal systems, including intestinal lavage fluid, vaginal lavage fluid, lung lavage fluid and saliva. The vaccine candidate also demonstrated good neutralizing activity and elicited good immune response.

Against influenza, vaccines containing the PIKA adjuvant can effectively reduce the viral load of animal respiratory tracts. They provided cross protection against multiple viruses and demonstrated good antiviral effects.

Yisheng’s chief medical officer, Zhongkai Shi, said a large number of preclinical and clinical trial results showed the advantages of PIKA adjuvant in new vaccine development.

“We hope that the PIKA-adjuvanted recombinant protein vaccine candidate can play an important role in combating the pandemic, especially for those with aging or defective immune systems,” he said.

Manufacturing and commercialization plans

Yisheng is ready to take its vaccine products to the market at home and abroad with its existing manufacturing facilities in China. It also has a manufacturing plant in the early design phase in Singapore.

“We have commercialization capacity and several hundred people actively manufacturing vaccine products,” Shao told BioWorld, adding that the company could manufacture up to a couple hundred million doses based on preliminary estimations.

While the initial focus will be on China and Southeast Asia, Shao said the company is actively looking for partners from the U.S., Europe or other countries.

“This is going to be a multi-country effort,” he emphasized, adding that Yisheng hopes to work with partners not only in clinical development, but also in manufacturing and commercialization to bring YS-SC2-010 to more markets where it is needed.

“If COVID-19 is going to be around for the next few years, definitely it’s impossible for a single company or just a handful of them to handle such a huge unmet demand at the global level,” he said.

To date, more than 10 Chinese companies are among those developing COVID-19 vaccines. They include Sinovac Biotech Ltd., Cansino Biologics Inc., Clover Biopharmaceuticals, Stemirna Therapeutics Co. Ltd., Beijing Advaccine Biotechnology, Chongqing Zhifei Biological Products Co. Ltd., Walvax Biotechnology Co., Ltd., Suzhou Abogen Biosciences Co. Ltd., Xiamen Innovax Biotech, Hualan Biological Engineering Inc., Zhejiang Pukang Biotechnology Co., Ltd., Changchun Bcht Biotechnology Co. and Wuhan Bravovax Co. Ltd.