Domestic antibodies are not afraid of Omicron, Tengsheng Bo Medicine: ready to deal with more mutations

Source of this article: Times Finance Author: Li Aohua

Like the Delta mutation that erupted in the spring, Omicron has left this winter's epidemic uncertain.

Image credit: pexels

On December 20, local time, the EPIDEMIC model data released by the US Centers for Disease Control and Prevention showed that as of December 18, the proportion of infection cases of the Olmi kerong variant strain had reached 73.2% of the total number of cases, and the Omilon had replaced Delta as the main epidemic strain in the United States.

This variant, which attracted widespread global attention about a month ago, combines a high transmission efficiency comparable to Delta and a very high probability of immune escape. According to data released by the Peking University research team on the preprint website BioRxiv, after analyzing the epitope distribution and escape of neutralizing antibodies in 247 viral spike protein RBD (receptor binding region), it was found that at least 85% of the new crown neutralizing antibodies were escaped by Omilon, and most of the neutralizing antibodies currently used urgently are ineffective against Omilton.

Tengsheng Bo Pharmaceutical has previously issued an announcement that the new in vitro chimeric virus experiment neutralization data show that its self-developed combination therapy of amphavir monoclonal antibody/romizumab (BRII-196/BRII-198 combination therapy) maintains the neutralizing activity of the new coronavirus variant strain Omilon, and is one of the few new coronavirus neutralizing antibodies that are basically unaffected by Omilton.

Times Finance learned from the online media conference of Tengsheng Bo Pharmaceutical held on the morning of December 21 that since there are as many as 15 important mutation sites in the RBD region of Aomi Kerong, BRII-196, which mainly targets the RBD region and the human receptor ACE2 binding site, has significantly reduced the neutralization ability of Aomi Kerong, briI-198 is basically unaffected by Aomi Kerong, and Zhu Qing, senior vice president of Tengsheng Bo Pharmaceutical and head of the biopharmaceutical department, stressed that in a high concentration environment, BRII-196 can still be effective in inhibiting the virus, so the combination therapy of the new crown neutralizing antibody of Tengsheng Bo medicine still maintains the neutralizing activity of Omi kerong.

At the close of the afternoon of the same day, Tengsheng Bo Pharmaceutical rose by 4.69%, and the total market value reached HK$24.922 billion.

Domestic neutralizing antibodies are not afraid of Opmi kerong

Tengsheng Bo Medicine's "debut record" of new crown neutralizing antibody combination therapy is amazing.

On December 8, the State Food and Drug Administration (NMPA) urgently approved the listing application for the combination therapy of new coronavirus neutralizing antibodies developed by a subsidiary of Tengsheng Bo Pharmaceutical for the treatment of mild and ordinary types, and adults and adolescents (12-17 years old, weighing ≥ 40 kg) who are at high risk of progressing to severe disease (including hospitalization or death), of which adolescent indications are conditionally approved. This is the first approved COVID-19 neutralizing antibody therapy in China.

The approval of the Temsex Drug COVID-19 Neutralizing Antibody Therapy is based primarily on a Phase 3 clinical trial supported by the National Institutes of Health (NIH). The results of the study showed that the combination of amphavir monoclonal antibody/romizumab reduced hospitalizations and deaths by about 80% compared with placebo (78% in the interim analysis), making it the best performer of its kind of approved therapy worldwide.

However, in the context of the epidemic of Omilon, whether neutralizing antibody therapy can effectively resist Omilon is the focus of more attention.

Among the neutralizing antibody therapies that have been approved so far, only the antibody therapies of Tengshengbo Drugs and GSK maintain neutralizing activity against at least 9 mutant strains such as alpha, beta, and gamma at the same time. In the face of the menacing Omilon, only Tengsheng Bo medicine and GSK antibody therapy have resisted the pressure.

In the early stage of designing dual antibody therapy, considering that the new crown virus is an RNA virus with a high probability of mutation, Tengsheng Bo Medicine decided to choose combination therapy and use two antibodies against different binding sites to reduce the chance of immune escape after the virus mutates. Among them, BRII-196 targets the site where the viral spike protein RBD region binds to human ACE2 to block the binding of the virus to human cell receptors, while BRII-198 acts after binding to the RBD region and ACE2.

"Picking 2 out of more than 200 antibodies may be just a numbers game for everyone, but we were very tangled in the selection process." Because it is necessary to take into account the different positions of these two antibody drugs that bind to the virus and play different roles at different stages, under the mutual cooperation of such a set of 'combination fists', the pair of antibodies can play the role we expect when inhibiting the virus into the cell process and responding to the emergence of mutant strains. Zhang Linqi, professor at Tsinghua University School of Medicine and director of the Center for Global Health and Infectious Diseases Research and COMPREHENSIVE AIDS Research at Tsinghua University, told Times Finance, "It is a very wise decision to think about it now, and we are also pleased with such a result." ”

How to deal with future mutations?

For all R&D enterprises related to the new crown virus, the constantly mutating virus is like a "time bomb", and new mutant strains are always influencing the pattern of market competition.

Up to now, only the combination therapy of amphavir monoclonal/romizumab, which was independently developed by Tengsheng Bo Pharmaceuticals, and sotrovamab, a monoclonal therapy developed by GSK and VirBio, are still effective against Omiclon.

In terms of small molecule oral drugs, Annaliesa Anderson, senior vice president of Pfizer, recently said that the company is confident that the oral drug PAXLOVID developed by the company is effective in the prevention and control of the Amicoreon strain.

It is understood that PAXLOVID obtained a license from the European Medicines Agency on December 16, local time, and in an emergency, EU member states can use the drug to treat adult patients with new crown who do not need auxiliary oxygen, but the disease develops into an adult patient with severe illness and higher risk.

Small molecule oral drugs are more convenient to use than antibody therapy via intravenous injection. However, in the view of Luo Yongqing, CEO of Tengsheng Huachuang, antibodies and small molecule oral drugs have different application scenarios.

"The role of neutralizing antibodies is the full management of the disease, which can be complementary to the vaccine during the prevention phase. The results of the study showed that the body's antibody levels at the 9th month were comparable to the peak after the third dose of vaccine, that is, at least for more than 9 months after the injection of amphexumab/romizumab combination therapy. In addition to the preventive effect, it can prevent mild to moderate patients from developing into severe patients. The advantage of small molecule drugs is that they are convenient to take orally, but they need to be used for 5 days, mainly to inhibit viral replication. Neutralizing antibodies basically come from the human body and are safer; small molecules are synthetic and take a long time to determine safety. Both classes of drugs have their own characteristics, and it is difficult to predict future market share. Luo Yongqing said.

In addition, in the nearly 20 months of research and development of Tengsheng Bo Pharmaceutical, thousands of monoclonal antibodies have been stockpiled to cope with unknown new coronavirus mutations.

"The degree of mutation in Omikeron is astonishing. Mutations in viruses are random, and scientists are studying the origin of these mutations, as well as the laws by which they arise, hoping to make a judgment in advance on future mutations of the virus in order to evaluate existing and alternative antibodies. Zhang Linqi said.

Zhu Qing pointed out that according to the current accumulated experience, the new crown virus mutation is very rapid, and can not predict, from the perspective of antibody research and development, the most important thing is to find antibodies that can be used for broad-spectrum treatment, its binding site should be in a conservative sequence more places, while there must be high activity, which is the first consideration of the second generation of product research and development. In addition, at present, the main binding site of the antibody is in the RBD part, and the study of other binding sites also needs to be further optimized.