Eight months after Beijing-based Yisheng Biopharma Co. Ltd. unveiled its recombinant protein vaccine candidate for COVID-19, YS-SC2-010, the company raised $130 million in a series B round to pave the way for the vaccine to enter clinical trials in the second quarter of this year, company CEO David Shao told BioWorld.

The financing arrived almost nine years after Yisheng’s June 2012 series A round, as the COVID-19 pandemic sparked investors’ interest in vaccine companies. Oceanpine and Orbimed co-led the round, getting on board with other investors such as Eightroad, F-Prime Capital, 3W Capital, Hillhouse Capital, Adjuvant Capital, MSA Capital, AIHC, Epiphron Capital, Superstring Capital and Haitong International.

Shao said the series B round will help advance Yisheng’s clinical programs, most notably YS-SC2-010, and step up its manufacturing capacity.

“The [YS-SC2-010] program is going well. We’re still at the preclinical stage, so hopefully in the next few months this program can move to clinical development,” he said. Based on animal models, it appears the candidate could induce sustainable immune response for at least six months, he added.

“Hopefully, we can initiate the clinical study of our COVID-19 vaccine program in the second quarter of this year in multiple countries; then, in the second half of this year, we can have more clinical data from this program,” he said.

Given the reduced number of COVID-19 cases in China, Shao said the company is considering carrying out the clinical trials in multiple regions, possibly in Southeast Asia and the Middle East, as well as Australia.

Similar to the technology that Novavax Inc. uses to develop NVX-CoV2373, YS-SC2-010 is based on a trimeric recombinant protein and incorporates a full-length S protein-based trimeric antigen. Coupled with Yisheng’s PIKA (polyinosinic-polycytidylic acid-based adjuvant) technology, YS-SC2-010 is expected to induce a quick and prolonged immune response in humans.

Another Chinese vaccine developer adopting a similar technology is Sichuan Clover Biopharmaceuticals Inc., which also closed a series B this week, raising $230 million to move its protein-based COVID-19 vaccine SCB-2019 to phase II/III by June this year.

A PIKA pipeline

A long-time player established in 2002, Yisheng is trying to differentiate itself from other vaccine developers with its PIKA immunomodulating technology, which it uses to develop immune drugs and vaccines to tackle rabies, hepatitis B, shingles, influenza and coronavirus.

The PIKA technology augments both innate and adaptive immune responses through the TLR3, RIG-I and MDA5 pathways. Endosomal double-stranded (dsRNA) can be recognized by TLR3 while cytosolic dsRNA can be sensed by the RIG-I-like receptor family that includes RIG-I and MDA-5.

Through TLR3, RIG-I and MDA-5 signaling, the PIKA technology can induce a prompt production of interferon, cytokines, chemokines and costimulatory factors. Hence, the technology can enable development of biotherapeutics based on TLR3, RIG-I and MDA5 activation.

Before Yisheng turned its focus to the PIKA technology for drug and vaccine development, it already launched a rabies vaccine known as the YSJA rabies vaccine, the first alum-free lyophilized rabies vaccine marketed in China. The vaccine has served over 16 million patients for post-exposure protection against rabies since 2003.

Known as a rabies vaccine specialist, Yisheng is now developing a new one with the PIKA technology. Soon to enter a global phase III trial, the PIKA rabies vaccine is the most advanced candidate in its pipeline. It is said to be able to accelerate post-exposure immune protection.

“It has a superior profile compared to other rabies vaccines on the market,” Shao explained. “It can provide sufficient protection within the first seven days, instead of waiting for 28 days to get the protection from the standard rabies vaccine. So basically, we reduce the vaccination time from one month down to one week.”

Besides the COVID-19 vaccine program, the series B round will also support clinical trials for the PIKA rabies vaccine in China and outside China. “We pretty much finished phase I in China, from which the data looks very promising… In the next few weeks, we will make an announcement about our phase I study in China,” he told BioWorld.

“Outside China, we also finished phase I and phase II studies, so we’re about to start a global, multicenter phase III trial in the next few months,” he added.

New funds from the series B will also help Yisheng step up its manufacturing capacity. “We’re constructing a manufacturing plant not just for the COVID-19 vaccine, but also for the rabies vaccine. The [fund] will help us complete our plant construction as soon as possible,” Shao said.

Yisheng can now produce 20 million doses a year for the rabies vaccine, he revealed, and it plans to produce as many as 100 million doses for the COVID-19 vaccine.

Designed with the PIKA technology, other products in clinical development include YS-HBV-001, a preventive hepatitis B vaccine with a short duration regimen, and YS-ON-001 for treating advanced solid tumors. Candidates in the preclinical and discovery stages include PIKA YS-HBV-002 for chronic hepatitis B and PIKA YS-ON-002 for solid tumors.

Yisheng is headquartered in China, with operations in the U.S. and Singapore with more than 500 employees.