Global new coronary pneumonia treatment urgently needs a breakthrough

During the National Day holiday, a news about Merck's anti-new coronary pneumonia oral drug Molnupiravir (Monellavir, referred to as "Mo medicine") made everyone excited

However, just after the festival, reports and information came from India that the drug "has no significant effect" on patients with moderate Covid-19, as if the same ladle of cold water was poured on our heads

At present, the treatment of new coronary pneumonia has risen to be a strategic issue for advanced medical countries, and Eglin's new anti-inflammatory drug EG-009A is achieving breakthroughs through a six-point development strategy

1.

What is certain is that the research and development of Mo medicine is a major advancement in the history of human fight against the new crown pneumonia virus

However, the latest clinical research results from India show that monelavir is not very effective against moderate new coronary disease

The number of people in need of treatment (NNT) is a commonly used quantitative analysis tool to compare the harms and benefits of drugs

The mechanism and advantages of Mo medicine:

One of the reasons for the success of Moyao is its very different mechanism of interfering with virus replication: the disaster of virus coding

Mo medicine is metabolized in the body and becomes a ribonucleoside analogue

Being able to be taken orally is the biggest advantage of Mo medicine

Potential side effects of Mo medicine:

Since the theory of the drug's own mechanism is a lethal mutation, the exposure of the drug may cause mutations in the host's DNA during the host DNA replication process

Table 1.

2.

China, the United States, and Europe have entered the "post-vaccine era", with vaccinated populations exceeding 65%-70%, which is an indicator of herd immunity

A study by Pfizer, a US pharmaceutical company, found that half a year after completing its new coronavirus pneumonia (COVID-19) vaccination, the protection of the vaccine will be reduced from 88% to 47%, but the prevention of hospitalization and mortality will still be as high as 90%
.

Israel uses Pfizer's mRNA vaccine, and its effective rate is very high, reaching more than 95%
.
But after the vaccine injection rate exceeded 80%, 40% of breakthrough infections occurred, of which 20% required hospitalization and 10% required intensive treatment in the ICU
.
A survey of nearly 40,000 people in Los Angeles, the United States showed that breakthrough infections reached 25%, and the hospitalization rate was between 1% and 5%
.

In terms of consumption of medical resources, the number of ICU beds in the United States is 35 per 100,000 people, and in China it is about 3 per 100,000 people
.
From the cost point of view, the cost of patients entering the ICU in the United States is 320,000 US dollars, and ordinary inpatient treatment is 75,000 US dollars
.
If China calculates breakthrough infections based on the above data, it will be a very large amount of data
.
Once a major breakthrough infection occurs, China's treatment pressure is evident
.
Therefore, the new crown treatment drugs have extremely important significance for the treatment of patients and the stability of the entire society.
The Chinese government attaches great importance to them and incorporates it into the national strategy to pay attention
.

3.
Fighting COVID-19: What are we Eglin doing?

From a therapeutic point of view, none of the currently approved drugs, including the US EUA, treat pulmonary inflammation caused by new coronary pneumonia, and the products developed by Eglin Pharmaceutical include this indication
.
Among the treatment technologies developed globally, Eglin is taking the representative route of anti-inflammatory and adopting a brand-new anti-inflammatory mechanism
.
In the field of development strategy, we choose to develop in a “high regulatory” environment.
A simple understanding is to benchmark against higher drug regulatory standards in the United States, Europe, and Japan
.
We believe that only anti-new coronary pneumonia drugs developed under strict regulatory standards are likely to have outstanding performance in future patient penetration rates
.

4.
Where is the breakthrough point of Eglin's new anti-inflammatory drug EG-009A?

EG-009A will be used to treat the cytokine storm caused by the new coronavirus infection
.
It is an anti-inflammatory drug with a new mechanism, mainly used to treat moderate to severe new coronary pneumonia to reduce the mortality of patients
.

EG-009A is a selective glucocorticoid receptor modulator
.
Through multiple screening of 1,040 natural products and FDA-approved drugs, it was determined that EG-009A selectively regulates clinically significant GR target genes, including ENaC (epithelial sodium ion channel plays an important role in epithelial cell fluid balance), FKBP5 ( It is related to the decrease of GR sensitivity and the increase of resistance) and GILZ (anti-inflammatory or tumorigenesis)
.
This makes EG-009A have a good anti-inflammatory effect, while avoiding secondary infections, femoral head necrosis and other side effects, and can be used for long-term treatment
.

Human antibodies are the key to fighting the virus, but sometimes they will "out of control" and attack their own organs and tissues
.
In the mid-stage of the new coronavirus infection, the virus has generally stopped replicating, and moderate to severe patients have overactive immune responses, which may cause a "cytokine storm" (CRS) that harms the patients themselves
.
EG-009A can be inhibited in trans, in which the activated monomeric GR binds to other transcription factors (such as NF-κB and AP-1) to prevent the expression of its pro-inflammatory genes, thereby inhibiting excessive immune responses through multiple targets, Inhibit cytokine storm, such as reducing tumor necrosis factor, IL-6, IL-1β and G-CSF and other factors to treat moderate to severe new coronary pneumonia
.

Features and indications of EG-009A:

The treatment direction of EG-009A is moderate to severe new coronary pneumonia disease
.
As the name suggests, the infection of the new coronavirus to the lungs is very obvious, reaching 50%-80%
.
However, among the 10 EUAs approved by the FDA, there is no solution to the problem of pneumonia treatment
.
This is the entry point of Eglin Pharmaceutical EG-009A
.

We had two communication meetings with the FDA before, and finally reached the 5 hard-core indicators related to lung failure of the EG-009A treatment endpoint, namely: whether to use a ventilator, whether to use high-flow oxygen, and whether to use non-invasive positive Pressure ventilator, whether to use an extracorporeal membrane oxygenation machine (ECMO), and whether there are other typical clinical symptoms of lung failure
.

EG-009A has two dosage forms: oral and intramuscular injection, each with its own characteristics
.
The two dosage forms can be used separately or in combination
.
For example, first give a quick-acting injection to quickly increase the blood concentration, and then use an oral agent to maintain the blood concentration, which is convenient for patients to use
.

Accelerate development in a highly regulated environment:

The main reasons why Eglin Pharmaceutical chose to base its strategy on the "highly regulated" market are based on the following considerations
.
As a preventive vaccine, WHO's access committee distinguishes the review cycles of "high-regulated" and "low-regulated" countries
.
For example, the vaccine approved by Pfizer in the United States, the WHO approved it in one week
.
For China's vaccines, it took Sinopharm and Kexing five or six months to get the WHO certification
.
This is first of all a question of speed
.

More importantly, the WHO currently does not have a mature mutual recognition mechanism for therapeutic drugs, and it lacks sufficient influence on the approval of therapeutic drugs.
The latter actually still lags behind the drug regulatory authorities of many countries
.
Among countries, mutual recognition of therapeutic drugs is relatively feasible, especially products approved in "highly regulated" regions
.
Take Hong Kong as an example.
If a drug is approved in both the United States and Europe, its registration and application in Hong Kong will be very simple, and it will take about a few weeks to go on the market
.

In addition, the Eglin team has five former FDA review officers.
The accumulation of knowledge on regulations supports us to take the "high regulatory" route, not seeking WHO access, but seeking FDA or EUA approval
.
Through the advantages of "high regulation", we can avoid some uncertainties and accelerate the globalization
.

In general, the development direction of our new crown therapeutic drugs is in line with the national strategy, and our thinking follows the clinical value chain.
We implement research and development and advancement in the principle of "combination boxing", hoping to make breakthroughs in unsatisfied treatment fields.
, To contribute to the global prevention and control of the new crown epidemic
.