CanSino announces clinical data on inhaled and intramuscular vaccines

On December 29, CanSino Biologics Co.
, Ltd.
voluntarily disclosed the results
of recent clinical research on inhaled new crown vaccine and intramuscular new crown vaccine.

CanSino Biologics Co.
, Ltd.
(hereinafter referred to as the "Company") inhaled recombinant novel coronavirus vaccine (adenovirus type 5 vector) (hereinafter referred to as "inhaled new coronavirus vaccine") and intramuscular recombinant new coronavirus vaccine (5 A number of extended clinical studies have been carried out on adenovirus vectors) (hereinafter referred to as "intramuscular new crown vaccine") and O-strain/original bivalent inhaled new crown vaccines, and phased data
have been obtained.
Due to the many unpredictable factors in the process of drug clinical trials, the results and timing of clinical trials, reviews and approvals have certain uncertainties, so investors are advised to make prudent decisions and pay attention to preventing investment risks
.
The relevant situation is hereby announced as follows:

First, the basic information of the product

Up to now, the company's intramuscular new crown vaccine has been conditionally approved for 18 in China People aged and older, approved for sequential booster immunization, and at the same time obtained emergency use authorization/conditional marketing in many countries abroad, are included in the World Health Organization (WHO) Emergency Use List (EUL).

The company's inhaled coronavirus vaccine has been included in emergency use in China as a booster shot for people aged 18 and over, and has obtained emergency use authorization
in Morocco.
Intramuscular and inhaled vaccines have been recommended as second booster doses
.
The O-strain/primitive bivalent inhaled new crown vaccine was developed against the Omicron variant and is still in the clinical research stage
.

2.
Relevant information and main results of clinical research

1.
Carry out recombinant novel coronavirus vaccine in adults aged 18 years and older who have completed 3 doses of inactivated new crown vaccine (5 Randomized, open-label, parallel-controlled clinical study of immunogenicity and safety of sequential enhancement of adenovirus vectors

The clinical study was initiated in April 2022 and conducted in Jiangsu, with a total of 360 enrollments and long-term follow-up
.
Study settings recruit 3 doses of inactivated vaccine previously administered at intervals of 6 Subjects were given booster immunization for months, and subjects were randomly assigned to the inhaled new crown vaccine group, the intramuscular new crown vaccine group or the inactivated vaccine group (hereinafter referred to as the "inhalation group", "intramuscular injection group" and "inactivated group") according to 1:1:1, each group was approximated 120 people
.
All subjects were systematically observed for safety within 28 days after vaccination and samples were collected on the day of vaccination, 14 days, 28 days, 3 months, and 6 months after vaccination for immunogenicity evaluation
.

(1) Security

The overall incidence of adverse reactions within 28 days of exemption in the inhalation group was 9.
40%, which was lower than that of the control group
.
Adverse reactions in the inhalation group were mainly grade 1, with an incidence of 5.
98%, grade 2 3.
42%, and no occurrence3 Grade adverse reactions
.
No SAE report
within 6 months of booster vaccination.
Overall safety results showed 3 doses previously given A booster dose of inhaled COVID vaccine is safe in people with inactivated vaccine, especially in the elderly
.

(2) Immunogenicity

The test results of the original true virus neutralizing antibody showed that on the basis that the level of the pre-antibody was close to negative, the GMT of the inhaled antibody reached 672 28 days after the booster vaccination, which was higher than the 583 in the intramuscular group, which was much higher 59
in the inactivated group.
The inhalation group was approximately 11-fold
larger than the inactivated group.
Cross-neutralization test of Omicron BA.
5 pseudovirus using clinical trial serum, inhalation group immunity 28 days after neutralizing antibody junction GMT 108, much higher than homologous reinforcement of 19 in the inactivated group, with an antibody titer of 81% ≥16 and 20%
in the inactivated group.

2.
A study to evaluate the safety and immunogenicity of two recombinant novel coronavirus vaccines (adenovirus type 5 vector) in people aged 6~17 years

The clinical study was launched in April 2022 and was carried out in Beijing and Hunan, with a total of 360 People are enrolled and long-term follow-up
is being carried out.
The study set up a basic immunization group and a booster immunization group
.
The primary immunization group recruits 6~17 who have not received any new coronavirus vaccine years old, receive two doses of inhaled new crown vaccine; The booster immunization group recruited subjects aged 6~17 who had completed 2 doses of inactivated vaccine for at least 3 months, and randomly vaccinated inhaled new crown vaccine, intramuscular new crown vaccine or inactivated vaccine (hereinafter referred to as "inhaled group", "intramuscular group" and "inactivated group")
according to the ratio of 3:1:1.
The safety subgroup was set up to evaluate laboratory safety indicators, and the cell immunity subgroup and immune persistence subgroup
were also set up.

(1) Security

People aged 6~17 years old are exempt from the inhalation group 28 The overall incidence of adverse reactions within days was 15.
91%, which was lower than that of the control group
.
The adverse reactions in the inhalation group were mainly grade 1, and grade 3 was only 0.
45%.

No special safety risks
were identified during the study.

(2) Immunogenicity

The results of ELISAS-RBD IgG antibody test showed that the levels of pre-antibody free in the 3 groups were balanced.
All were close to the lower limit of detection, and 28 days later, the antibody GMT of the inhaled group reached 4,967 BAU/ml, which was higher than the 3528 BAU/ml in the intramuscular injection group and much higher than that of the inactivated group 411 BAU/ml, about 12 times
that of the inhalation group compared to the inactivated group.

3 months after booster immunization, antibody levels in the inhaled group were still maintained at a high level of 3380 BAU/ml, which was 12.
4 times that of the inactivated group, and the antibody levels in the inhaled group were much higher than those in WHO standard serum （1000BAU/ml）
。

Results of neutralizing antibodies to the original true virus showed that on the basis of baseline all being close to negative, booster immunization was 28 Day, the antibody GMT reached 462 in the inhaled group, which was higher than 350 in the intramuscular group, much higher than 47 in the inactivated group, and about 10 times
higher in the inhaled group than in the inactivated group.

A neutralization test of Omicron BA.
5 pseudovirus using study serum showed that 28 days after booster immunization, the antibody GMT reached 409 in the inhaled group, which was higher than 261 in the intramuscular group and much higher than in the inactivated group 46.
The inhalation group is about 9 times
larger than the inactivated group.

3.
Clinical trial of bivalent inhaled recombinant novel coronavirus variant vaccine (adenovirus type 5 vector) in adults aged 18 years and older

The clinical study was initiated in September 2022 and conducted in Chongqing, with a total of 450 people enrolled and long-term follow-up
.
Studies were 18 years of age and older who had been vaccinated 3 A randomized, blinded, parallel-controlled trial of people who received inactivated COVID-19 vaccine ≥ 3 months between the last doses, in which all subjects received one dose of O at the same time in a 1:1:1 ratio Strain/original strain bivalent inhaled new crown vaccine, O strain monovalent inhaled new crown vaccine or original strain monovalent inhaled new crown vaccine (hereinafter referred to as "bivalent vaccine group", "O strain monovalent vaccine group", "original strain monovalent vaccine group").

Each group planned to recruit 150 participants, for a total of 450 People, of which ≥ 60 years old about 30
%.
All subjects were systematically observed for safety within 28 days of vaccination and on the day of vaccination, 14 days, 28 days, 2 months, 3 months, 4 months, 6 Samples were collected monthly for humoral immunological, cellular immunity, and mucosal immunoassays
.

(1) Security

Within 28 days after exemption, the overall incidence of adverse reactions in the bivalent vaccine group, the original monovalent vaccine group and the O strain monovalent vaccine group were 15.
89%, 14.
67% and respectively 22.
00%, there was no statistical difference
between the three.
The adverse reactions were mainly grade 1 (incidence 10.
00%~15.
33%), and the incidence of grade 2 adverse reactions was 3.
31%~6.
67%, Grade 3 adverse reactions occurred only 1 case (fever) in the bivalent vaccine group, and the incidence occurred 0.
66%
。 The overall safety results showed that one booster dose of inhaled new crown vaccine was safe in people who had received 3 doses of inactivated vaccine in the past, and there was little difference between different inhaled new crown vaccine groups
.

(2) Immunogenicity

Humoral immunity: 28 days after booster vaccination on the basis of close negative levels of free prebodies, bivalent vaccine group, original monovalent vaccine group, and O The GMTs of the original true virus neutralizing antibody in the monovalent vaccine group were 245, 288 and 104, respectively.
The BA.
1 variant euvirus neutralizing antibody GMT was 44, 30 and 33; BA.
5, respectively The germant euvirus neutralizing antibody GMTs were 30, 22, and 19
, respectively.
Overall, antibody levels in bivalent vaccines are advantageous
.

Cellular immunity: Peripheral blood PBMC cytokine levels (O-strain peptide library stimulation)
were measured using ELISPOT.
28 days after booster vaccination, bivalent vaccine group, original monovalent vaccine group and O-strain monovalent vaccine group IFN-γ levels were 75, 60 and 82Spots/105PBMC, with positivity rates of 100%, 82% and 90%,
respectively.
Bivalent vaccine cellular immunity has advantages
.

Mucosal immunity: use the MSD method to detect sIgA levels in nasal swab samples (against multiple variants).

The results suggest that inhaled new crown vaccines can induce broad-spectrum sIgA for different variants Reaction, antibody levels increased by 6~9 times compared with before the exemption, and the differences between different vaccine groups were not obvious
.

3.
Risk warning

1.
The conditional marketing application of intramuscular injection new crown vaccine is based on the Administrative Measures for Drug Registration (Order No.
27 of the State Administration for Market Regulation Article 63: During the clinical trial of drugs, drugs that meet the following circumstances may apply for conditional approval: (3) Vaccines urgently needed to respond to major public health emergencies or other vaccines determined to be urgently needed by the National Health Commission, and the benefits are assessed to outweigh the
risks.
”

In accordance with Article 20 of the Vaccine Administration Law of the People's Republic of China, if a particularly major public health emergency or other emergency seriously threatens public health occurs, the competent health department under the State Council shall propose the emergency use of the vaccine according to the needs of the prevention and control of infectious diseases, and it may be used
urgently within a certain scope and period after the organization and approval of the drug regulatory department under the State Council.

2.
There is uncertainty
about the application of intramuscular new crown vaccine and inhaled new crown vaccine in people aged 6-17 years old, and whether the O/original strain bivalent inhaled new crown vaccine can obtain emergency use or marketing approval at home and abroad.

3.
After inquiry, up to now, 13 new crown vaccines in China have been approved by the National Food and Drug Administration for conditional marketing or emergency use, 3 have been included in the emergency use list of the World Health Organization, and many others are in the clinical trial stage
.
The company's future market sales of new crown vaccines will still face fierce competition, and at the same time affected by various factors such as the development and changes of the epidemic at home and abroad, the new crown vaccination rate and immunization strategies
.

4.
Please make prudent decisions and pay attention to preventing investment risks
.
The relevant company information shall be
subject to the announcements published in the company's designated disclosure media "China Securities News", "Securities Times", "Securities Daily", "Shanghai Securities News" and the website of the Shanghai Stock Exchange.

Resources:

www.
cansinotech.
com.
cn