Ascletis announces positive Phase I clinical results for the new crown oral RdRp inhibitor ASC10

Ascletis Pharmaceuticals Limited (HKEx: 1672, "Ascletis") announced positive top-line data
from the Multi-dose-Escalation (MAD) Phase I study (NCT05523141) of the oral polymerase (RdRp) inhibitor ASC10 in healthy subjects on December 12.
ASC10 is an innovative oral dual prodrug with a new, differentiated chemical structure
compared to monoprodrug monoravir.
After oral administration, both ASC10 and monoravir are rapidly and completely converted in the body to the same active drug, ASC10-A, also known as β-D-N4-hydroxycytidine (NHC).

The two-prodrug strategy significantly increased the oral bioavailability of the active ASC10-A
.

Phase I data showed that ASC10 at all doses, including 800 mg twice daily, was safe and well tolerated in Chinese subjects
.
Safety data were similar
between the ASC10 treatment group and the placebo treatment group.
The exposure of the active drug ASC10-A in Chinese subjects after 800 mg twice daily in Chinese subjects was 94% of the exposure of ASC10-A after monodrug monoravir in Japanese subjects and ASC10-A after twice-daily administration[1].

After administration of 800 mg, plasma concentrations of double prodrug ASC10 in Chinese subjects were below the lower detection limit (0.
2 ng/ml).

Similarly, plasma concentrations of the single prodrug monoravir in US subjects are negligible after administration of 800 mg[2].

After weight adjustment, the exposure to the active drug ASC10-A after administration of 800 mg of dual prodrug ASC10 in Chinese subjects and 800 mg of monoprodrug monoravir in US subjects was also comparable [2].

Food had no effect on ASC10-A exposure, suggesting that ASC10 could be taken with food or on an empty stomach
.

Monoravir has been approved or authorized for emergency use
in many countries, including Japan and the United States.
In addition, recent literature has shown that monoravir has an exciting clinical effect in Chinese patients with Omicron infection [3].

Based on Ascletis ASC10 Phase I results and clinical efficacy data on monoravir in patients in the United States [4], Japan, and China, the ASC10 registration clinical trial dose was selected to be 800 mg twice daily
.

The active drug ASC10-A has potent antiviral activity
against a variety of Omicron variants such as BA.
5 and BA.
2.
75.
Ascletis has filed several patent applications
worldwide for ASC10 and its uses.
The ASC10 oral tablets used in this clinical study were developed by Ascletis proprietary technology
.

"Phase I clinical results show that ASC10 has a very good safety profile and high
druggability in Chinese subjects.
I believe ASC10 is expected to play an important role
in the fight against the pandemic.
Professor Qiu Yunqing, Executive Vice President of the First Affiliated Hospital of Zhejiang University School of Medicine and principal investigator of the ASC10-I phase clinical trial, said
.

"Phase I clinical data have clarified the druggability
of ASC10 for new crown indications.
ASC10 has filed patent applications around the world, and we look forward to ASC10's contribution
to the fight against the epidemic in China and overseas.
" Dr.
Jinzi Wu, Founder, Chairman of the Board and Chief Executive Officer of Ascletis, said
.

       [1] Nakamura et al.
, Clin Transl Sci.
2022;00:1–12

       [2] Painter et al.
, Antimicrobial Agents and Chemotherapy, May 2021, Volume 65, Issue 5, e02428-20

       [3] Zou et al.
, Frontiers in Pharmacology, June 2022, Volume 13, Article 939573

       [4] Bernal et al.
, The New England Journal of Medicine, December 16, 2021