my country's new coronavirus special medicine may produce another "dark horse" that can prevent mutant strains!

0.6 grams of antibody per injection, one injection lasts for one month!

At Beijing Ditan Hospital, COVID-19 patients received a "compassionate use drug" called DXP-604, which was independently developed in my country. After using it, the viral load in the patients dropped significantly, and symptoms such as shortness of breath and loss of taste and smell improved significantly. Some patients have recovered and been discharged from the hospital.

The front-line clinical performance makes DXP-604 likely to become a "dark horse" specific drug for COVID-19. What's more unique is that while most other candidate drugs use "a pair of antibodies" to prevent the novel coronavirus from escaping, DXP-604 has achieved the goal of using "a single antibody" to prevent mutant strains.

The drug was jointly developed by Peking University's Xie Xiaoliang team and Danshen Biotechnology. On November 16, a Science and Technology Daily reporter exclusively interviewed the leader of the research and development team, Peking University Lee Shau Kee Chair Professor Xie Xiaoliang. He said that the characteristics of a single antibody replacing an "antibody pair" make its production cost less than one-third of other candidate drugs. At present, Danshen has reached a cooperative development intention with Sinopharm Group China Biologics.

What does the new coronavirus special medicine look like?

DXP-604 is a neutralizing antibody drug, and its prototype is the neutralizing antibody that already exists in the human body. After fighting the new coronavirus, the patient's own immune mechanism will select the neutralizing antibodies that "can fight".

This step is considered a "wide selection", and the special medicine is among them. The problem is that the special medicine must be selected from the best! In the past, it took years to select the best antibodies, because the number of neutralizing antibodies is huge, tens of thousands, and it is impossible to capture trace amounts. The invention of high-throughput single-cell gene sequencing technology allows researchers to quickly search cells one by one.

As a pioneer in single-cell genomics, Xie Xiaoliang's laboratory has a leading international technological advantage. In the global race for research and development, antibody drug development is like panning for gold in the sand. The more stones you turn over, the more likely you are to capture the strongest antibody.

The Peking University team screened more than 8,000 candidate antibodies in just a few months. Data showed that based on multiple screenings, the Peking University team screened out multiple effective candidate drugs, and DXP-604 was one of the best.

That’s why only 0.6 grams of the drug is needed for treatment, and even less is possible. “We are doing a ramp-up experiment, and it’s very likely that 0.3 grams will be enough,” Xie Xiaoliang said.

How to prevent virus escape?

The development of novel coronavirus drugs is changing rapidly! In the past 22 months, global resources have gathered rapidly; in the past few months, a large number of candidate drugs have failed due to frequent mutations of the virus.

The repeated and complex COVID-19 outbreaks have put forward higher requirements for COVID-19 specific drugs to cope with mutations. Antibody pairing is a common strategy. Two antibodies have different binding sites with the virus. When one antibody fails, the other can still inhibit the virus. For example, Regeneron and Eli Lilly both used antibody pairs, but one of their antibodies escaped the Delta strain.

"We have a drug candidate DXP-593, which was escaped by the Delta strain." Xie Xiaoliang said that its efficacy is very high, but it has exerted tremendous evolutionary pressure on the virus, causing the amino acid sequence of the new coronavirus to change and the antibodies to become ineffective.

The cost of escaping was heavy. Xie Xiaoliang did not hide the fact that nearly 100 million yuan of R&D funds had gone down the drain.

What to do? Xie Xiaoliang's team originally planned to use DXP-593 and DXP-604 together, but a new research method brought an unexpected surprise. DXP-604 alone can prevent mutant strains.

"We have recently developed a high-throughput yeast display technology, which allows us to test all 4,000 possible single-point mutations in the receptor-binding domain of the SARS-CoV-2 protein (S protein) with neutralizing antibodies one by one." Xie Xiaoliang said that the new technology can clearly show the possibility of SARS-CoV-2 escape in different antibody drugs.

The "escapes" that occurred in the real world were verified one by one. For example, the candidate drugs that failed in the two multinational pharmaceutical companies mentioned above also showed in the test results that they would escape at the delta mutation site.

The test results of DXP-604 were unexpected, and it presented the novel coronavirus with a dilemma: either it does not mutate and is neutralized by DXP-604, or it mutates out of the circle, but changes so much that it is difficult to bind to human cells. The "killer weapon" of DXP-604 is to put the novel coronavirus in a situation where it will either die if it does not mutate or seek death if it mutates.

To verify the results, the team also collaborated with a third-party team to use a fake virus platform to conduct a real mutation escape "battle," and the results were consistent.

What is the launch plan for Super Antibody?

"It is the super antibody we are looking for." Looking back at the twists and turns along the way, Xie Xiaoliang concluded that antibody-specific drugs are not all-round, the more "strong" the better. Being too strong will cause the virus to mutate and be reborn. DXP-604 is just right at the competitive site, and ultimately "practicing Tai Chi" leaves the virus with no way out and dying.

"We have a full-spectrum antibody that can resist all single-point mutations in the RBD region. It is sufficient to neutralize all existing variants and to the greatest extent prevent future variants from escaping," said Xie Xiaoliang.

Regarding the clinical trial and launch schedule of DXP-604, Xie Xiaoliang introduced that domestic Phase II clinical trials are being carried out, and contact has been made with Sinopharm Group China Biologics to promote overseas Phase II/III clinical trials. Beijing has approved DXP-604 as a "compassionate use drug" for clinical treatment in Beijing Ditan Hospital. Currently, the drugs for clinical trials and "compassionate use drugs" are all produced by WuXi Biologics. Xie Xiaoliang expressed the hope that my country's independently developed special drugs for COVID-19 will be available soon.

◎ Science and Technology Daily reporter Zhang Jiaxing

Source: Science and Technology Daily

Editor: Wang Yu

Reviewer: Wang Xiaolong

Final review: Liu Haiying