Ascletis announced that it has submitted a clinical trial application for the monkeypox indication of the oral antiviral drug ASC10 in the United States

Ascletis Pharmaceuticals Limited (HKEx: 1672, "Ascletis") announced on October 26 that it has submitted an application
for a New Drug Clinical Trial (IND) for ASC10, an oral inhibitor candidate for monkeypox virus polymerase, to the U.
S.
Food and Drug Administration (FDA).

ASC10 is an oral and broad-spectrum antiviral dual prodrug with a new chemical structure
that differentiates from the single prodrug molnupiravir.
After oral administration, both ASC10 and monupivir can be rapidly and completely converted in vivo to the same active metabolite, ASC10-A, also known as β-D-N4-hydroxycytidine (NHC) or EIDD-1931
.
Ascletis has filed several patent applications worldwide for ASC10 and its use in the treatment of viral diseases, including the treatment of monkeypox virus infection
.

Experimental data in an in vitro monkeypox virus infection cell model showed that ASC10-A had potent antiviral activity against monkeypox virus, indicating that ASC10 was expected to be an effective treatment
for monkeypox virus infection.
The study was commissioned by Ascletis to carry out the IIT Institute, which is headquartered at
the Illinois Institute of Technology in Chicago, USA.

In August 2022, Dr.
Watashi et al.
of the National Institute of Infectious Diseases in Tokyo, Japan, published a research paper ^[1].

Dr.
Watashi et al.
tested a total of 132 drugs in the study, and the results showed that monupivir (the active metabolite ASC10-A) and two other drugs had potent antiviral activity
in a monkeypox virus infection cell model.
The remaining 129 drugs such as remdesivir, favipiravir, sofosbuvir and ribavirin, had no activity
against monkeypox virus.

Monkeypox virus belongs to the genus Orthopoxvirus and can cause disease similar to smallpox symptoms^[2].

According to the World Health Organization (WHO), as of October 26, 2022, there have been more than 75,000[3^] confirmed cases worldwide, and monkeypox virus has spread in more than 100 countries ^[3].

Of these, a total of 28,061 ^[4] confirmed cases
of monkeypox/orthopoxvirus have been reported in the United States.
On 19 September 2022, China reported its first confirmed case
of monkeypox virus infection.
WHO assesses Europe and the Americas as areas at high risk for monkeypox virus ^[3].

By employing a dual prodrug strategy, ASC10 was 3.
2 and 2.
1 times
higher than that of monupivir in Caco-2 cells (human colorectal adenocarcinoma cells) and active metabolite exposure in monkeys, respectively.
Studies have shown ^[5,6] that ASC10-A is resistant to multiple Omicron variants (BA.
1 EC50=0.
3 μM; BA.
2 EC50=0.
25 μM； BA.
5 EC50=0.
23 μM； BA.
2.
75 EC50=0.
90 μM) has potent cellular antiviral activity
.
At present, the phase Ib clinical trial in the new crown patient is being carried out
in the United States.

"As a leading biotechnology company in the field of antivirals in China, Ascletis is committed to using scientific research to solve the challenges
posed by viral diseases.
Currently, there is no treatment
for monkeypox virus infection worldwide.
The submission of the ASC10 monkeypox indication clinical trial application in the United States will further broaden the Ascletis virus disease pipeline and provide a potential therapy
for monkeypox virus infection.
Dr.
Jinzi Wu, founder, chairman of the board and CEO of Ascletis, said
.

       [1] Daisuke Akazawa, Hirofumi Ohashi, Takayuki Hishiki, et al.
Potential anti-monkeypox virus activity of atovaquone, mefloquine, and molnupiravir, and their potential use as treatments.
bioRxiv preprint.
https://doi.
org/10.
1101/2022.
08.
02.
502485

       [2] #tab=tab_1

       [3] https://worldhealthorg.
shinyapps.
io/mpx_global/

       [4]

       [5] Takashita E, Yamayoshi S, Fukushi S, et al.
Efficacy of Antiviral Agents against the Omicron Subvariant BA.
2.
75.
N Engl J Med.
2022; 387(13): 1236-1238

       [6] In-house studies