HONG KONG – China’s Shanghai Junshi Biosciences Co. Ltd. has struck a deal with Merck KGaA for a clinical trial program in China to investigate the efficacy and safety of Junshi’s anti-PD-1 monoclonal antibody (MAb), Tuoyi (toripalimab) in combination with Merck’s Erbitux (cetuximab) as a treatment for recurrent and/or metastatic squamous cell carcinomas of the head and neck (SCCHN).

Tuoyi is the first domestically marketed PD-1 monoclonal antibody in China. According to the company, more than 30 toripalimab mono and combo clinical trials have been conducted worldwide for more than 10 tumor types and have demonstrated positive antitumor outcomes.

Merck’s Erbitux is an IgG1 monoclonal antibody that specifically targets the EGFR. It is believed to have a synergistic mechanism of action in SCCHN treatment.

"Research has shown that anti-PD-1 combination therapy could enhance clinical efficacy of anti-PD-1 MAb, and that the future direction of tumor treatment will increasingly focus on combination therapy, using multiple mechanisms of action to fight tumors,” said Ning Li, the CEO of Junshi.

“Merck's cetuximab, which has been approved for treatment of SCCHN, is one of the ideal drug candidates for combined use with anti-PD-1 drugs,” he added. “We look forward to benefiting more patients with the combination of targeted therapy and immunotherapy in the treatment of SCCHN."

COVID-19 efforts

Another significant progression for Junshi is its development of neutralizing antibodies (NAbs) as a potential treatment for COVID-19.

Junshi and its partner, Eli Lilly and Co., have isolated two specific human monoclonal antibodies (CA1 and CB6) from a recovered COVID-19 patient.

Though both antibodies showed substantial neutralization activity in vitro against the novel coronavirus, it was found that CB6 had superior neutralizing potential.

“A neutralizing antibody is an antibody capable of keeping an infectious agent, usually a virus, from infecting a cell by neutralizing or inhibiting its biological effect. It could potentially facilitate virus clearance, altering the course of infection,” Jun Xiong, the chairman of Junshi, told BioWorld.

He said he believes antibody-based therapies have several advantages. “They can be therapeutic as well as prophylactic, for instance in protecting health workers in a high-risk environment; they are generally safe given their specificity to the pathogen; and compared with the serum of recovered patients, the antibodies are more consistent in quality and can be readily mass-produced through biological engineering, thereby ensuring ample supply to treat the pandemic,” said Xiong.

According to animal testing results published in Nature, CB6 reduced virus levels by about 3 logs in rhesus monkeys when administered one day after infection. It was also able to show strong prophylactic protection by keeping the viral load at no more than 103 RNA copies/ml when given one day before viral challenge.

“The fact that CB6 can protect rhesus monkeys from COVID-19 infection suggests a potential for prophylactic use in humans," said Daniel Skovronsky, the chief scientific officer of Lilly and president of Lilly Research Laboratories. "We are moving as quickly as possible to test such a protective effect in patients at risk for COVID-19."

However, Xiong admits that there is still some way to go. “The monkey may be the best animal model for SARS-CoV-2, but it's still not human,” he said.

The companies intend to file an IND and initiate clinical trials in the U.S. and China in the second quarter of 2020. “The clinical trial will start in June and will last three to five months,” said Xiong.

Under their partnership, Lilly will receive an exclusive license to conduct the clinical development, manufacturing and distribution of products outside of greater China. Junshi will maintain its rights in greater China.

In exchange, Lilly will pay Junshi an up-front fee of $10 million, and milestone payments of up to $245 million upon achieving prescribed events, plus double-digit royalties on the net sales of the product. Lilly will also subscribe to Junshi’s new H shares to the amount of $75 million.

The potential COVID-19 treatment represents a new area for Junshi.

“We had four disease areas before: oncology, metabolic, auto-immunity and neurologic. And now, infectious disease has become our fifth area,” said Xiong.

“At the beginning of the COVID-19 outbreak, Junshi rapidly launched a research and development program to study neutralizing antibodies to combat COVID-19,” Xiong noted. “Within two months, the company has completed IND-enabling preclinical studies, process development, and production for GLP toxicity study and GMP production of clinical material by leveraging the company's platform technology.”

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